Information on EC 2.4.2.8 - hypoxanthine phosphoribosyltransferase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
2.4.2.8
-
RECOMMENDED NAME
GeneOntology No.
hypoxanthine phosphoribosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
reaction mechanism
Q8R7L0
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
kinetic mechanism
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ordered bi-bi mechanism
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ordered bi-bi mechanism
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
catalytic mechanism
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
catalytic mechanism
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
catalytic mechanism
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
active site structure
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
active site structure
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
active site structure
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
residues I99-L121 form the catalytic loop
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
Thr47 binds diphosphate
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
essential role of Ser95-Tyr96 dyade in catalysis
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
kinetic model
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
during catalysis a long flexible loop closes over the active site, functional role
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
guanine and 6-mercaptopurine can replace hypoxanthine
-
-
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ordered bi bi kinetic mechanism with 5-phospho-alpha-D-ribose 1-diphosphate binding first followed by the purine base
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ordered bi bi reaction mechanism, formation of dead-end complexes with purine substrates and diphosphate
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
reaction mechanism, function and influence of invariant active site loop I residues on enzyme efficiency in forward and reverse reaction
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
reaction mechanism, the flexible loop II, comprising 12 amino acid residues, closes over the active site of the enzyme as it approaches the transition state, the loop is required for full activity, structure-function relationship for the conserved residues
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
residue F36 is responsible for substrate specificity, structure-function relationship
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
residue L44 is responsible for substrate specificity, structure-function relationship
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
sequential mechanism with 5-phospho-alpha-D-ribose 1-diphosphate binding first, active site helix comprising D137-D153 with key active site residues K68, D137, and K165, substrate binding sites and structures, overview
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
substrate binding structure and mechanism, a non-proline cis-peptide may be essential for activity
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
binding structure involving residue K68 at the AB-dimer interface and residues V96 and D97 of the opposing subunit, overview. Residues E133 and D137 block the binding of 5-phospho-alpha-D-ribose 1-diphosphate, mechanism, overview
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ordered reaction mechanism, 5-phospho-alpha-D-ribose 1-diphosphate-Mg2+ binds first followed by the purine base. After the covalent reaction, diphosphate then dissociates from the complex and the nucleoside monophosphate is released in the rate-limiting step
-
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
ordered reaction mechanism. The substrates bind in a functionally ordered fashion, with 5-phospho-alpha-D-ribose 1-diphosphate binding first in the forward direction and IMP or GMP first in the reverse reaction, transition state structure and 5'-phosphate binding structure on HGPRT, overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pentosyl group transfer
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenine and adenosine salvage III
-
-
adenine and adenosine salvage IV
-
-
Biosynthesis of secondary metabolites
-
-
Drug metabolism - other enzymes
-
-
guanine and guanosine salvage
-
-
guanine and guanosine salvage II
-
-
Metabolic pathways
-
-
Purine metabolism
-
-
purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
IMP:diphosphate phospho-D-ribosyltransferase
Guanine and 6-mercaptopurine can replace hypoxanthine.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6-hydroxypurine phosphoribosyltransferase
-
-
-
-
6-mercaptopurine phosphoribosyltransferase
-
-
-
-
GMP pyrophosphorylase
-
-
-
-
guanine phosphoribosyltransferase
-
-
-
-
guanine-hypoxanthine phosphoribosyltransferase
-
-
-
-
guanosine 5'-phosphate pyrophosphorylase
-
-
-
-
guanosine phosphoribosyltransferase
-
-
-
-
guanylate pyrophosphorylase
-
-
-
-
guanylic pyrophosphorylase
-
-
-
-
HGPRT
-
-
-
-
HGPRTase
-
-
-
-
hypoxanthine-guanine phosphoribosyltransferase
-
-
-
-
IMP pyrophosphorylase
-
-
-
-
IMP-GMP pyrophosphorylase
-
-
-
-
inosinate pyrophosphorylase
-
-
-
-
inosine 5'-phosphate pyrophosphorylase
-
-
-
-
inosinic acid pyrophosphorylase
-
-
-
-
inosinic pyrophosphorylase
-
-
-
-
phosphoribosyltransferase, 6-mercaptopurine
-
-
-
-
phosphoribosyltransferase, hypoxanthine
-
-
-
-
purine-6-thiol phosphoribosyltransferase
-
-
-
-
transphosphoribosidase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9016-12-0
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
at least 3 charge variant isoforms
-
-
Manually annotated by BRENDA team
in MDCK cells
-
-
Manually annotated by BRENDA team
2 charge variant isoforms with different substrate specificities
-
-
Manually annotated by BRENDA team
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes; strain K12
-
-
Manually annotated by BRENDA team
Escherichia coli K12
strain K12
-
-
Manually annotated by BRENDA team
strain Portland I, 3 charge variant forms
-
-
Manually annotated by BRENDA team
Giardia intestinalis Portland
strain Portland I, 3 charge variant forms
-
-
Manually annotated by BRENDA team
3 charge variant forms
-
-
Manually annotated by BRENDA team
construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes
-
-
Manually annotated by BRENDA team
gene HPRT
-
-
Manually annotated by BRENDA team
gene HPRT
UniProt
Manually annotated by BRENDA team
Japanese population
-
-
Manually annotated by BRENDA team
purified enzyme
-
-
Manually annotated by BRENDA team
parasites isolated from rabbits
-
-
Manually annotated by BRENDA team
gene hgprt
SwissProt
Manually annotated by BRENDA team
gene HPRT
-
-
Manually annotated by BRENDA team
inbred strain C57BL/6J
-
-
Manually annotated by BRENDA team
construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes
-
-
Manually annotated by BRENDA team
hyperthermophile
-
-
Manually annotated by BRENDA team
3 charge variant forms
-
-
Manually annotated by BRENDA team
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes; strain LT-2
-
-
Manually annotated by BRENDA team
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
strain LT-2
-
-
Manually annotated by BRENDA team
single gene locus, two alternative-splicing-derived isozymes HXGPRT-I and HXGPRT-II
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
P00492
a deficiency in HPRT activity leads to overproduction of uric acid, hyperuricemia, with gouty arthritis, nephrolithiasis, and mild neurologic symptoms. According to the degree of enzymatic deficiency, a large spectrum of neurologic features can also be observed, ranging from mild or no neurologic involvement to complete Lesch-Nyhan disease
malfunction
-
complete deficiency of hypoxanthine-guanine phosphoribosyltransferase causes the Lesch-Nyhan disease, a genetic disorder associated with motor and psychiatric disturbance and self-injurious behaviour, the role of serotonin receptor 2C, HTR2C, might be involved, overview
malfunction
-
HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype, and is involved in Lesch-Nyhan disease pathogenesis
malfunction
-
mutations in the gene encoding the purine biosynthetic enzyme HPRT cause the resulting intractable and largely untreatable neurological impairment of Lesch-Nyhan disease. The disorder is associated with a defect in basal ganglia DA pathways, phenotype mechanisms analysis in human embryonic carcinoma neurogenesis model, overview
physiological function
-
HPRT is a housekeeping enzyme responsible for recycling purines, it regulates early developmental programming of dopamine neurons
physiological function
-
the enzyme enables the reutilization of purine base adenine converting it to mononucleotide AMP, substrate for the synthesis of high-energy nucleotides
physiological function
-
the enzyme is involved in the specification and development of neurons, including dopaminergic neurons, as well as in the regulation of dopaminergic transcription factors, overview
physiological function
-
the purine salvage enzyme HGXPRT is essential for purine nucleotide and hence nucleic acid synthesis in the malaria parasite
physiological function
-
production of enzyme-deficient human Coxsackievirus-induced pluripotent stem cells and human HUES11 embryonic stem cells using shRNA. Both cells show >99% enzyme knock-down and demonstrate markedly decreased expression of the purinergic P2Y1 receptor mRNA. In Coxsackievirus-induced cells, P2Y1 mRNA and protein down-regulation by hypoxanthine phosphoribosyltransferase knockdown is refractory to activation by the P2Y1 receptor agonist ATP and shows aberrant purinergic signaling, as reflected by marked deficiency of the transcription factor pCREB and constitutive activation of the MAP kinases phospho-ERK1/2. Moreover, hypoxanthine phosphoribosyltransferase-knockdown Coxsackievirus-induced cells also demonstrate marked reduction of phosphorylated beta-catenin
physiological function
-
treatment of cells with guanosine and GMP results in statistically significant decreases in cell growth after 48 h and 72 h in the melanoma cell line C32 and in the U-87 glioma cell line. Presence of hypoxanthine blocks the antiproliferative effects. Hypoxanthine phosphoribosyltransferase-negative cell line C32-TG cells completely has lost the inhibitory response to guanine treatment. Hypoxanthine phosphoribosyltransferase silencing by siRNA is able to partially block the guanine-induced antiproliferative effects in U-87 glioma cell lines
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-amino-6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
2-amino-6-mercaptopurine ribotide + diphosphate
show the reaction diagram
-
-
-
-
?
2-hydroxy-6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
2-hydroxy-6-mercaptopurine ribotide + diphosphate
show the reaction diagram
-
-
-
-
?
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
6-mercaptopurine ribotide + diphosphate
show the reaction diagram
-
-
-
-
?
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
6-mercaptopurine ribotide + diphosphate
show the reaction diagram
-
-
-
-
?
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
6-mercaptopurine ribotide + diphosphate
show the reaction diagram
-
-
-
?
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
6-mercaptopurine ribotide + diphosphate
show the reaction diagram
-
-
-
-
?
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
thioinosinic monophosphate + diphosphate
show the reaction diagram
-
a thiopurine antimetabolite
a therapeutically active metabolite
-
-
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
6-thioinosine monophosphate + diphosphate
show the reaction diagram
-
-
-
-
?
6-thioguanine + 5-phospho-alpha-D-ribose 1-diphosphate
6-thio-GMP + diphosphate
show the reaction diagram
-
-
-
-
?
8-azahypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
8-aza-IMP + diphosphate
show the reaction diagram
-
-
-
-
?
allopurinol + 5-phospho-alpha-D-ribose 1-diphosphate
allopurinol ribonucleoside 5'-monophosphate + diphosphate
show the reaction diagram
-
-
-
?
allopurinol + 5-phospho-alpha-D-ribose 1-diphosphate
allopurinol ribonucleoside 5'-monophosphate + diphosphate
show the reaction diagram
-
low activity
-
?
GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
P00492
-
-
-
?
GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Q26997
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Q9NJI5
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Q8R7L0
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
P20035
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Q5SLS3
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Q97W22
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes, and catalyse the 2 reactions with different specificities
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
binds hypoxanthine 67-times less effectively than guanine and 4-times less effectively than xanthine
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
absolutely specific for guanine
diphosphate binds at Thr70, diphosphate-binding loop sequence: LTGA
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
guanine is utilized more rapidly than hypoxanthine
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
6-oxopurine salvage pathway reaction
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
salvage synthesis
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
P00492
wild-type enzyme, no activity with mutant F36L
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
hypoxanthine and guanine preferred substrates
-
-
ir
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
wild-type and chimeric mutant enzyme
modeling of GMP binding to the chimeric enzyme
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
P20035
wild-type and chimeric mutant enzyme
modeling of GMP binding to the chimeric enzyme
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Giardia intestinalis Portland
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Escherichia coli K12
-
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes, and catalyse the 2 reactions with different specificities
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Q97W22
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes, and catalyse the 2 reactions with different specificities
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q26997
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q9NJI5
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
P20035
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q5SLS3
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q97W22
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
most effective substrate
diphosphate is bound by Thr47
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
unlike the hypoxanthine-guanine phosphoribosyltransferase from other sources this enzyme binds hypoxanthine 67-times less effectively than guanine and 4-times less effectively than xanthine
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
equilibrium lies far in direction of IMP formation
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
equilibrium lies far in direction of IMP formation
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes, and catalyse the 2 reactions with different specificities
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
2 assay methods
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
binds hypoxanthine 67-times less effectively than guanine and 4-times less effectively than xanthine
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
no activity with hypoxanthine
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
6-oxopurine salvage pathway reaction
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q8R7L0
6-oxopurine salvage pathway reaction
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
salvage synthesis
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
binding mechanism and structure of IMP occupying the diphosphate site, overview
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q8R7L0
hypoxanthine is the preferred substrate
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
P00492
wild-type enzyme, no activity with mutant F36L
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
the enzyme is involved in the purine salvage pathway
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
hypoxanthine and guanine preferred substrates, continuous spectrophotometric enzyme assay, pH 7.5, 12 mM MgCl2, 40-70C, 30 sec
Kd(diphosphate): 4.7 +/-0.1 mM, revealed by quenching of intrinsic fluorescence of the enzyme upon diphosphate-binding
-
ir
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
wild-type and chimeric mutant enzyme
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
P20035
wild-type and chimeric mutant enzyme
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Giardia intestinalis Portland
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Escherichia coli K12
-
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes, and catalyse the 2 reactions with different specificities
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q97W22
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes, and catalyse the 2 reactions with different specificities
-
?
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
P00492
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
-
low activity
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
-
wild-type enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
P00492
mutant F36L, no activity with the wild-type enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
-
-
-
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
Q26997
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
Q97W22
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
no activity
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
no activity
-
-
-
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
no activity
-
-
-
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
no activity
-
-
-
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
poor substrate
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
recombinant chimeric mutant DS1
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
the enzyme also performs the reaction of xanthine phosphoribosyltransferase, EC 2.4.2.22
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
low catalytic efficiency (kcat/KM), xanthine is not preferred but a usable substrate
-
-
ir
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
-
wild-type human enzyme does not accept xanthine as substrate, mutant F36L does catalyze the conversion of xanthine to XMP with a kcat much lower than those of hypoxanthine and guanine
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
Giardia intestinalis Portland
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
Escherichia coli K12
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
Q97W22
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
P20035
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
-
wild-type and chimeric mutant enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
P20035
wild-type and chimeric mutant enzyme
-
-
?
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
-
-
-
-
additional information
?
-
-
forward reaction: transfer of the phosphoribosyl group to N9 position of 6-oxopurines
-
-
-
additional information
?
-
-
9-deazaguanine is no substrate
-
-
-
additional information
?
-
-
no substrates: 5-formamido-4-imidazolecarboxamide, uric acid, 8-azaguanine, 2,6-diaminopurine, orotic acid, phosphate
-
-
-
additional information
?
-
-
dynamic and conformational properties of purified enzyme alone, in complex with GMP and Mg2+, and in equilibration mixture of enzyme with IMP, Mg2+/diphosphate and hypoxanthine, Mg2+/5-phosphoribosyl 1-diphosphate, and in transition-state analogue complex of enzyme, immucillin-GP and Mg2+/diphosphate
-
-
-
additional information
?
-
-
a mentally retarded child and its asymptomatic uncle have a partial enzyme deficiency, homozygous, while mother and grandmother are heterozygous and not enzyme-deficient
-
-
-
additional information
?
-
-
no substrate: adenine
-
-
-
additional information
?
-
-
no substrate: adenine
-
-
-
additional information
?
-
-
no substrate: adenine
-
-
-
additional information
?
-
-
kinetic study
-
-
-
additional information
?
-
-
kinetic study
-
-
-
additional information
?
-
-
kinetic study
-
-
-
additional information
?
-
-
kinetic study
-
-
-
additional information
?
-
-
no incorporation of xanthine in vivo, salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
Q9NJI5
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
locus of Lesch-Nyhan syndrome, activator of the prodrugs 6-mercaptopurine and allopurinol
-
-
-
additional information
?
-
-
enzyme is essential for salvaging exogenous purine bases
-
-
-
additional information
?
-
-
enzyme is essential for salvaging exogenous purine bases
-
-
-
additional information
?
-
Q9NJI5
enzyme is essential for salvaging exogenous purine bases
-
-
-
additional information
?
-
-
the enzyme activity is regulated by stabilization and destabilization of the enzyme through release or binding of product and substrates, overview
-
-
-
additional information
?
-
-
formation of dead-end complexes with purine substrates and diphosphate
-
-
-
additional information
?
-
-
L67 side chain participates in hydrophobic interactions between dimer subunits important for the proper positioning of main chain atoms that influence enzyme chemistry and the binding of 5-phospho-alpha-D-ribose 1-diphosphate, diphosphate, and hypoxanthine, residue 69 needs to be small like Gly, which is found there, to avoid sterical interference with binding of 5-phospho-alpha-D-ribose 1-diphosphate and diphosphate as well as the positioning of a metal ion
-
-
-
additional information
?
-
-
substrate binding induces conformational changes required for catalysis
-
-
-
additional information
?
-
-
the conformation of the flexible loop, containing a 3-10 helix and a unique double serine repeat, is important for substrate binding and activation of the enzyme
-
-
-
additional information
?
-
P00492
the flexibilty of loop IV can influence the substrate specificity
-
-
-
additional information
?
-
-
the purified recombinant enzyme shows very low activity
-
-
-
additional information
?
-
-
enzyme-deficiency is involved in development of gout
-
-
-
additional information
?
-
-
the enzyme is organized in a branched bi-enzyme system with xanthine oxidase, EC 1.17.3.2
-
-
-
additional information
?
-
-
the parasite depends on the human host purine salvage pathway enzyme hypoxanthine guanine xanthine phosphoribosyltransferase for survival, because it does not have a de novo pathway for synthesis of nucleotides on its own
-
-
-
additional information
?
-
-
the two isozymes exhibit similar substrate specificity, kinetic characteristics, and temporal expression patterns, overview
-
-
-
additional information
?
-
-
no formation of PRPP and 6-oxopurine by pyrophosphorylysis due to disability of binding to nucleotides IMP, GMP, XMP at 40-70C and substrate concentrations of up to 0.5 mM
-
-
-
additional information
?
-
-
substrate binding structure involving residue K68 at the AB-dimer interface and residues V96 and D97 of the opposing subunit, overview. Residues E133 and D137 block the binding of 5-phospho-alpha-D-ribose 1-diphosphate, mechanism, overview
-
-
-
additional information
?
-
-
the binding site for the 5'-phosphate is located at residues 132-141
-
-
-
additional information
?
-
-
The substrates bind in a functionally ordered fashion, with 5-phospho-alpha-D-ribose 1-diphosphate binding first in the forward direction and IMP or GMP first in the reverse reaction, transition state structure and 5'-phosphate binding structure on HGPRT, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
P00492
-
-
-
?
GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
-
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
P20035
-
-
-
?
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
6-oxopurine salvage pathway reaction
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
salvage synthesis
-
-
r
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
GMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
-
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
P20035
-
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
6-oxopurine salvage pathway reaction
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
Q8R7L0
6-oxopurine salvage pathway reaction
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
salvage synthesis
-
-
r
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
the enzyme is involved in the purine salvage pathway
-
-
?
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
IMP + diphosphate
show the reaction diagram
-
-
-
-
?
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
P00492
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
-
low activity
-
-
r
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
-
wild-type enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
P00492
mutant F36L, no activity with the wild-type enzyme
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
-
-
-
-
?
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
P20035
-
-
-
?
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
-
-
-
-
r
additional information
?
-
-
no incorporation of xanthine in vivo, salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
Q9NJI5
salvage incorporation of exogenous purine nucleotides, no de novo synthesis
-
-
-
additional information
?
-
-
locus of Lesch-Nyhan syndrome, activator of the prodrugs 6-mercaptopurine and allopurinol
-
-
-
additional information
?
-
-
enzyme is essential for salvaging exogenous purine bases
-
-
-
additional information
?
-
-
enzyme is essential for salvaging exogenous purine bases
-
-
-
additional information
?
-
Q9NJI5
enzyme is essential for salvaging exogenous purine bases
-
-
-
additional information
?
-
-
the enzyme activity is regulated by stabilization and destabilization of the enzyme through release or binding of product and substrates, overview
-
-
-
additional information
?
-
-
enzyme-deficiency is involved in development of gout
-
-
-
additional information
?
-
-
the enzyme is organized in a branched bi-enzyme system with xanthine oxidase, EC 1.17.3.2
-
-
-
additional information
?
-
-
the parasite depends on the human host purine salvage pathway enzyme hypoxanthine guanine xanthine phosphoribosyltransferase for survival, because it does not have a de novo pathway for synthesis of nucleotides on its own
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
absolute requirement; maximal activity at: 0.5-1 mM MgCl2
Mg2+
-
Km: 0.04-0.05 mM; maximal activity at: 1 mM; required
Mg2+
-
required
Mg2+
-
absolute requirement for Mg2+ or Mn2+
Mg2+
-
activating effect of Mn2+ is higher than that of Mg2+
Mg2+
-
maximal activity at: 1-10 mM; required
Mg2+
-
required
Mg2+
-
required
Mg2+
-
at 12 mM
Mg2+
-
required
Mg2+
-
required for binding of 5-phospho-alpha-D-ribose 1-diphosphate, binding via side chains of Glu101 and Asp102 and water molecules in the apoenzyme, binding site structure
Mg2+
-
dependent on
Mg2+
-
a divalent cation is required for activity
Mg2+
-
activates
Mn2+
-
can replace Mg2+; Km: 0.015-0.020 mM
Mn2+
-
absolute requirement for Mg2+ or Mn2+
Zn2+
-
activates, can replace Mg2+, Km: 0.066-0.075 mM
Mn2+
-
activating effect of Mn2+ is higher than that of Mg2+
additional information
-
no activation by Ca2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1S)-1-(9-deazaguanin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol 5-phosphate
-
-
(1S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol 5-phosphate
-
-
(3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]propyl)phosphonic acid
-
competitive. 466fold lower affinity for human enzyme. Treatment of cultured parasites with the bis-pavalate of the inhibitor as a prodrug inhbits growth with an IC50 of 45 microM
(R)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
-
(R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-bromoguanine
-
-
(R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
(S)-9-[2-(phosphonomethoxy)propyl]guanine
-
-
(S)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-azaguanine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-bromoguanine
-
-
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
; is toxic to cells and arrests cell growth
2-Amino-6-mercaptopurine
-
competitive to hypoxanthine
5-phospho-alpha-D-ribose 1-diphosphate
-
product inhibition
5-phospho-alpha-D-ribose 1-diphosphate
-
competitive against GMP; product inhibition
5-phospho-alpha-D-ribose 1-diphosphate
-
competitive versus diphosphate and GMP or IMP
6-Chloropurine
-
-
6-Mercaptopurine
-
competitive to hypoxanthine
6-methylheptyl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
-
6-Thioguanine
-
competitive to hypoxanthine
6-Thioguanine
-
competitive to hypoxanthine
6-thioinosine
-
-
9-beta-Arabinofuranosylhypoxanthine
-
-
9-[2-(2-phosphonoethoxy)ethyl]guanine
-
-
9-[2-(2-phosphonoethoxy)ethyl]hypoxanthine
-
-
9-[2-(phosphonomethoxy)-3-fluoro-propyl]guanine
-
-
9-[2-(phosphonomethoxy)ethyl]-6-thioguanine
-
-
9-[2-(phosphonomethoxy)ethyl]-7-deaza-8-azahypoxanthine
-
-
9-[2-(phosphonomethoxy)ethyl]-8-azaguanine
-
-
9-[2-(phosphonomethoxy)ethyl]-8-bromoguanine
-
-
9-[2-(phosphonomethoxy)ethyl]guanine
-
; is toxic to cells and arrests cell growth
9-[2-(phosphonomethoxy)ethy]-8-hydroxyguanine
-
-
acyclic nucleoside phosphonates
-
analogues of the nucleotide reaction product, comprising a purine base joined by a linker to a phosphonate moiety, inhibitor design and potencies, overview. The inhibitors are selectivity for the enzyme of the human parasite Plasmodium falciparum, up to factor 58, compared to the human enzyme, overview
acyclic nucleoside phosphonates
-
analogues of the nucleotide reaction product, comprising a purine base joined by a linker to a phosphonate moiety, inhibitor design and potencies, overview. Selectivity for the parasite enzyme of up to 58 compared to the Homo sapiens enzyme, overview, design of potent and selective acyclic nucleoside phosphonates inhibitors of Plasmodium falciparum HGXPRT as antimalarial drug leads
adenine
-
no inhibition
AMP
-
no inhibition
AMP
-
mutant K134S, competitive
Azaguanine
-
-
Ba2+
-
-
Ca2+
-
strong
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
is toxic to cells and arrests cell growth
diethyl dicarbonate
-
alkylation of Arg155, complete inactivation at pH 9.0, pH dependent
diphosphate
-
-
diphosphate
-
product inhibition
diphosphate
-
competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, uncompetitive versus hypoxanthine or guanine
GMP
-
mixed inhibition
GMP
-
product inhibition
GMP
-
product inhibition
GMP
-
competitive against 5-phospho-alpha-D-ribose 1-diphosphate; product inhibition
GMP
-
competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, noncompetitive versus guanine
GMP
-
0.3 mM, 50% inhibition of guanine phosphoribosyltransferase activity
Guanine
-
substrate inhibition
Guanine
-
competitve against hypoxanthine
Guanine
-
competitive
Guanine
-
0.06 mM, 50% inhibition of hypoxanthine phosphoribosyltransferase activity
guanine ribose 5'-phosphate
-
-
Hg2+
-
complete inhibition at 3 mM after 3 min at 0C
hypoxanthine
-
substrate inhibition
hypoxanthine
-
competitive against guanine
hypoxanthine
-
competitive
hypoxanthine
-
0.16 mM, 50% inhibition of guanine phosphoribosyltransferase activity
hypoxanthine ribose 5'-phosphate
-
-
immucillin-G 5'-phosphate
-
active site contacts in the HGPRT/immucillin-G 5'-phosphate/diphosphate complex, overview
immucillin-H
-
transition state analogue, binds tightly to the active site, inhibition mechanism and kinetics
immucillin-H 5'-phosphate
-
transition state analogue, binds tightly to the active site, inhibition mechanism and kinetics
immucillin-H 5'-phosphate
-
5'-phosphate binding structure on HGPRT, overview
IMP
-
product inhibition
IMP
-
product inhibition
IMP
-
competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, noncompetitive versus hypoxanthine
IMP
-
feedback inhibition, competitive versus 5-phospho-alpha-D-ribose 1-diphosphate, binding mode
Inosine
-
slight inhibition
KCl
-
no inhibition
KCl
-
inactivation
Nucleotides
-
all free 5'-nucleotides are inhibitory, 6-OH purine nucleotides are most inhibitory, while 6-NH2 purine only at high concentrations
-
p-chloromercuribenzoate
-
reversed by dithiothreitol or 2-mercaptoethanol
Pb2+
-
inhibits the enzyme in erythrocytes about 20% at 0.0005 mM and about 12% at 0.0001 mM, and participates in hemolysis, the intensity of which negatively correlates with the activity of phosphoribosyltransferases, HPRT inhibition as one of the mechanisms of lead toxicity
Pb2+
-
moderately inhibits both the enzyme in erythrocytes even at very low concentrations, and participates in hemolysis, the intensity of which negatively correlates with the activity of phosphoribosyltransferases, HPRT inhibition as one of the mechanisms of lead toxicity
Phenylglyoxal
-
irreversible, complete inactivation, alkylation of Arg155, GMP protects, no alkylation of mutant R155K
propan-2-yl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
-
purine nucleotides
-
-
-
purine nucleotides
-
and analogues, overview
-
Tetranitromethane
-
complete inactivation at pH 9.0, pH dependent, modifies Tyr96 in the active site
xanthine
-
weak, competitive
XMP
-
product inhibition
[(3S)-4-hydroxy-3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]butyl]phosphonic acid
-
competitive. 592fold lower affinity for human enzyme
-
Mg2+
-
inhibitory effects are noncompetitive against 5-phosphoribose 1-diphosphate
additional information
-
mechanism of product inhibition; no inhibition by ADP, ATP, dAMP, UMP, and UTP
-
additional information
-
overview: inhibition constant of purines and purine analogs
-
additional information
-
no effect of iodoacetate, phenylglyoxal, p-chloromercuribenzoate, acetic anhydride, ethyl dimethylaminopropylcarbodiimide/ammonium acetate, and diisopropyl fluorophosphate
-
additional information
-
product inhibition study, the substrates/products protect the enzyme against digestion by trypsin, especially hypoxanthine with diphosphate
-
additional information
-
no inhibition by EGTA
-
additional information
-
cytotoxicity studies using human lung carcinoma A549 cells at 37C. The binding site for the 5'-phosphate is located at residues 132-141. No inhibition by (R)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
additional information
Q97W22
the activity of HGXPRTase was unaffected by the triphosphates ATP, GTP, CTP or UTP
-
additional information
-
guanine phosphoribosyltransferase activity: IMP and AMP are not inhibitory at concentrations up to 0.6 mM, adenine and xanthine are not inhibitory at concentrations up to 0.5 mM. Adenine and xanthine do not inhibit hypoxanthine phosphoribosyltransferase activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
GMP
-
0.05 mM, at least 2fold stimulation, hypoxanthine phosphoribosyltransferase activity
IMP
-
0.2 mM, at least 2fold stimulation, hypoxanthine phosphoribosyltransferase activity
additional information
-
activation by substrate and product IMP, reversibly destabilizes the enzyme
-
additional information
-
hypoxanthine phosphoribosyltransferase activity is unaffected by AMP
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36L, with xanthine
0.0044
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36K, with hypoxanthine
0.0053
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.011
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36G, with hypoxanthine
0.015
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.0191
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
0.026
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
0.027
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36L, with hypoxanthine
0.0282
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.0015 mM, 60C
0.029
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36K, with guanine
0.03
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant wild-type enzyme, with hypoxanthine
0.031
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme, with hypoxanthine
0.032
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
0.032
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme
0.032
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme, with guanine
0.033
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.035
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant wild-type enzyme, with hypoxanthine
0.0369
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.0024 mM, 70C
0.041
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36L, with guanine
0.0412
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.0016 mM, 50C
0.0428
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.0009 mM, 40C
0.05
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.05
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant F36G, with guanine
0.063
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.076
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant wild-type enzyme, with guanine
0.079
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant wild-type enzyme, with xanthine
0.083
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant mutant G69S
0.1
5-phospho-alpha-D-ribose 1-diphosphate
-
-
0.102
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant L44F, with hypoxanthine
0.112
5-phospho-alpha-D-ribose 1-diphosphate
Q8R7L0
pH 7.4, 50C, with guanine
0.116
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant L44F, with guanine
0.116
5-phospho-alpha-D-ribose 1-diphosphate
Q8R7L0
pH 7.4, 37C, with guanine
0.119
5-phospho-alpha-D-ribose 1-diphosphate
Q8R7L0
pH 7.4, 37C, with hypoxanthine
0.123
5-phospho-alpha-D-ribose 1-diphosphate
Q8R7L0
pH 7.4, 25C, with hypoxanthine
0.125
5-phospho-alpha-D-ribose 1-diphosphate
Q8R7L0
pH 7.4, 25C, with guanine
0.132
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant mutant L67M
0.133
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 12 mM MgCl2
0.134
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
0.138
5-phospho-alpha-D-ribose 1-diphosphate
Q8R7L0
pH 7.4, 50C, with hypoxanthine
0.151
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant mutant L44F, with xanthine
0.185
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196D
0.2
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196Q
0.201
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 22C, recombinant wild-type enzyme, with guanine
0.327
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 12 mM MgCl2, in presence of 0.05 mM IMP
0.36
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 25C, recombinant enzyme, with guanine
0.5
5-phospho-alpha-D-ribose 1-diphosphate
-
natural mutant I137T
0.546
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 28C, recombinant chimeric mutant enzyme with substrate hypoxanthine
0.546
5-phospho-alpha-D-ribose 1-diphosphate
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme with substrate hypoxanthine
0.659
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196R
1.075
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 28C, recombinant chimeric mutant enzyme, with substrate guanine
1.075
5-phospho-alpha-D-ribose 1-diphosphate
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme, with substrate guanine
1.156
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196A
2.039
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 25C, recombinant enzyme, with hypoxanthine
0.035
5-phosphoribosyl 1-diphosphate
-
recombinant enzyme, with hypoxanthine
0.065
5-phosphoribosyl 1-diphosphate
-
recombinant enzyme, with guanine
0.127
5-phosphoribosyl 1-diphosphate
Q9NJI5
recombinant enzyme, with guanine
0.138
5-phosphoribosyl 1-diphosphate
Q9NJI5
recombinant enzyme, with hypoxanthine
0.0062
6-Mercaptopurine
-
-
0.0076
6-Thioguanine
-
-
0.36
8-Azahypoxanthine
-
-
0.0346
adenine
-
mutant K134S
0.0117
allopurinol
-
recombinant enzyme
0.135
allopurinol
-
recombinant enzyme
0.016
diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme, with IMP
0.0175
diphosphate
-
wild-type enzyme
0.022
diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme, with GMP
0.025
diphosphate
-
recombinant enzyme, with inosine monophosphate
0.035
diphosphate
-
wild-type enzyme
0.035
diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme
0.103
diphosphate
-
wild-type enzyme
0.135
diphosphate
-
pH 7.5, 37C, recombinant mutant L67M
0.214
diphosphate
-
pH 7.5, 37C, recombinant mutant G69S
0.324
diphosphate
-
wild-type enzyme, reverse reaction
0.968
diphosphate
-
mutant E196D
0.0225
GMP
-
wild-type enzyme, reverse reaction
0.029
GMP
-
pH 7.5, 37C, recombinant wild-type enzyme
0.001
Guanine
-
below
0.001
Guanine
-
pH 7.4, 22C, recombinant wild-type enzyme
0.0011
Guanine
-
-
0.0011
Guanine
-
-
0.0011
Guanine
-
recombinant chimeric mutant DS1
0.0011
Guanine
-
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.0011
Guanine
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.0014
Guanine
-
recombinant enzyme, with other purine
0.0018
Guanine
-
-
0.0019
Guanine
-
recombinant enzyme, with other purine
0.002
Guanine
-
-
0.002
Guanine
-
pH 7.4, 22C, recombinant mutant F36L
0.002
Guanine
-
pH 7.4, 22C, recombinant mutant L44F
0.0021
Guanine
-
native enzyme
0.0024
Guanine
-
-
0.0027
Guanine
-
-
0.0027
Guanine
-
native enzyme
0.0028
Guanine
Q9NJI5
recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
0.0029
Guanine
-
pH 7.4, 22C, recombinant mutant F36K
0.00326
Guanine
-
+/-0.00029 mM, 70C
0.0035
Guanine
-
recombinant enzyme
0.0045
Guanine
-
pH 7.4, 22C, recombinant wild-type enzyme
0.00485
Guanine
-
+/-0.00056 mM, 50C
0.005
Guanine
-
wild-type enzyme
0.005
Guanine
-
wild-type enzyme
0.0061
Guanine
-
pH 7.4, 22C, recombinant mutant F36G
0.0074
Guanine
Q5SLS3
pH 7.9, 25C
0.01
Guanine
-
wild-type enzyme
0.012
Guanine
-
mutant enzyme
0.012
Guanine
-
wild-type enzyme
0.012
Guanine
-
pH 7.5, 37C, recombinant wild-type enzyme
0.016
Guanine
-
wild-type enzyme
0.018
Guanine
-
-
0.022
Guanine
-
pH 7.5, 37C, recombinant mutant G69S
0.025
Guanine
-
pH 7.4, 25C, recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
0.028
Guanine
-
-
0.037
Guanine
-
-
0.134
Guanine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate, pH 8.5
0.2
Guanine
-
pH 9.0, 37C
0.362
Guanine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate
0.5
Guanine
-
-
0.00052
hypoxanthine
-
-
0.0009
hypoxanthine
-
recombinant enzyme, with other purine
0.001
hypoxanthine
-
below
0.001
hypoxanthine
-
with 6-mercaptopurine
0.001
hypoxanthine
-
wild-type enzyme
0.001
hypoxanthine
-
pH 7.4, 22C, recombinant wild-type enzyme and mutant L44F
0.0014
hypoxanthine
-
recombinant chimeric mutant DS1
0.0014
hypoxanthine
-
pH 7.4, 22C, recombinant wild-type enzyme
0.0016
hypoxanthine
-
-
0.0016
hypoxanthine
-
pH 7.4, 22C, recombinant mutant F36K
0.0018
hypoxanthine
-
pH 7.4, 22C, recombinant mutant F36G
0.0018
hypoxanthine
-
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.0018
hypoxanthine
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.0024
hypoxanthine
-
recombinant enzyme
0.0024
hypoxanthine
Q8R7L0
pH 7.4, 25C
0.0025
hypoxanthine
-
-
0.0027
hypoxanthine
Q8R7L0
pH 7.4, 50C
0.0028
hypoxanthine
-
mutant E196R
0.0031
hypoxanthine
-
recombinant enzyme, with other purine
0.0033
hypoxanthine
Q8R7L0
pH 7.4, 37C
0.0036
hypoxanthine
-
mutant E196Q
0.0037
hypoxanthine
-
native enzyme
0.0038
hypoxanthine
-
-
0.0038
hypoxanthine
-
wild-type enzyme
0.00388
hypoxanthine
-
+/-0.00033 mM, 40C
0.0039
hypoxanthine
Q5SLS3
pH 7.9, 25C
0.0042
hypoxanthine
-
recombinant enzyme
0.0044
hypoxanthine
Q9NJI5
recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
0.0044
hypoxanthine
-
pH 7.4, 22C, recombinant mutant F36L
0.0048
hypoxanthine
-
mutant enzyme
0.00483
hypoxanthine
-
+/-0.00049 mM, 60C
0.0049
hypoxanthine
-
mutant E196D
0.0052
hypoxanthine
-
-
0.0061
hypoxanthine
-
wild-type enzyme
0.0061
hypoxanthine
-
+/-0.00143 mM, 70C
0.0063
hypoxanthine
-
mutant E196A
0.0064
hypoxanthine
-
wild-type enzyme
0.00702
hypoxanthine
-
+/-0.00104 mM, 50C
0.0086
hypoxanthine
-
wild-type enzyme
0.0086
hypoxanthine
-
pH 7.5, 37C, recombinant wild-type enzyme
0.011
hypoxanthine
-
-
0.015
hypoxanthine
-
pH 9.0, 37C
0.0192
hypoxanthine
-
pH 7.5, 37C, recombinant mutant L67M
0.023
hypoxanthine
-
-
0.023
hypoxanthine
-
natural mutant I137T
0.0339
hypoxanthine
-
pH 7.5, 37C, recombinant mutant G69S
0.038
hypoxanthine
-
mutant K134S
0.05
hypoxanthine
-
pH 7.4, 25C, recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
0.06
hypoxanthine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate
0.126
hypoxanthine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate, pH 8.5
0.0024
IMP
-
wild-type enzyme
0.0147
IMP
-
mutant E196Q
0.016
IMP
-
pH 7.5, 37C, recombinant wild-type enzyme
0.027
IMP
-
pH 7.5, 37C, recombinant wild-type enzyme and mutant L67M
0.0726
IMP
-
mutant E196D
0.08
IMP
-
pH 7.5, 37C, recombinant mutant G69S
1.043
IMP
-
mutant E196A
0.0054
inosine monophosphate
-
recombinant enzyme
0.027
inosine monophosphate
-
wild-type enzyme
0.095
xanthine
-
+/-0.0084 mM, 70C
0.1012
xanthine
-
+/-0.0101 mM, 50C
0.17
xanthine
-
recombinant enzyme, with 5-phosphoribosyl 1-diphosphate, pH 8.5
0.261
xanthine
-
pH 7.4, 22C, recombinant wild-type enzyme
0.287
xanthine
-
pH 7.4, 22C, recombinant mutant F36L
0.3
xanthine
-
above, purified recombinant chimeric enzyme DS1
0.332
xanthine
-
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.332
xanthine
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.42
xanthine
-
recombinant enzyme, pH 8.5
0.853
xanthine
-
pH 7.4, 22C, recombinant mutant L44F
0.09
inosine monophosphate
-
wild-type enzyme
additional information
additional information
-
-
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
kinetics; Km values of mutant enzymes for hypoxanthine, guanine, diphosphate, 5-phosphoribosyl 1-diphosphate, inosine monophosphate
-
additional information
additional information
-
kinetics
-
additional information
additional information
-
kinetics; wild-type and mutant T47K
-
additional information
additional information
-
wild-type and mutants: Km values for substrates hypoxanthine, guanine, xanthine, IMP, GMP, XMP
-
additional information
additional information
-
Km-values of mutant enzymes
-
additional information
additional information
-
-
-
additional information
additional information
-
Km-values, loop II-deletion mutant
-
additional information
additional information
-
kinetic analysis in the forward and reverse reaction of the wild-type enzyme and diverse mutant enzymes, overview
-
additional information
additional information
-
steady-state kinetics and dissociation constants
-
additional information
additional information
-
-
-
additional information
additional information
-
kinetic analysis of the branched bi-enzyme system, detailed overview
-
additional information
additional information
-
no significant change in KM with temperature (40-70C) for all substrates tested
-
additional information
additional information
-
steady-state kinetics
-
additional information
additional information
-
steady-state kinetics, recombinant enzyme, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0139
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 25C, recombinant enzyme, with guanine
0.48
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.02, 50C
0.66
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.03, 40C
0.97
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 25C, recombinant enzyme, with hypoxanthine
1.68
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.06, 60C
2.5
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
2.8
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196R
3.05
5-phospho-alpha-D-ribose 1-diphosphate
-
+/-0.07, 70C
4.26
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 12 mM MgCl2
4.7
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant mutant L67M
10.9
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196Q
14.2
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196D
20
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant mutant G69S
20.3
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196A
23.2
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme
23.2
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant enzyme, with hypoxanthine
32.2
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, recombinant enzyme, with guanine
36.3
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
74.8
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme, forward reaction
0.05
5-phosphoribosyl 1-diphosphate
-
loop II-deletion mutant
23.2
5-phosphoribosyl 1-diphosphate
-
wild-type enzyme
0.002
diphosphate
-
loop II-deletion mutant
0.041
diphosphate
-
wild-type enzyme
0.1
diphosphate
-
pH 7.5, 37C, recombinant enzyme, with GMP
0.12
diphosphate
-
pH 7.5, 37C, recombinant mutant L67M
0.31
diphosphate
-
pH 7.5, 37C, recombinant mutant G69S
0.33
diphosphate
-
mutant E196D
0.47
diphosphate
-
pH 7.5, 37C, recombinant enzyme, with IMP
0.477
diphosphate
-
wild-type enzyme
0.48
diphosphate
-
pH 7.5, 37C, recombinant wild-type enzyme
90
diphosphate
-
wild-type enzyme
0.09
GMP
-
pH 7.5, 37C, recombinant enzyme
5.8
GMP
-
wild-type enzyme, reverse reaction
0.013
Guanine
-
purified recombinant chimeric enzyme DS1
0.039
Guanine
-
loop II-deletion mutant
0.14
Guanine
-
pH 7.4, 25C, recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
0.21
Guanine
-
+/-0.01, 50C
0.37
Guanine
-
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.37
Guanine
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme
1.1
Guanine
-
pH 7.4, 22C, recombinant mutant L44F
1.2
Guanine
-
pH 7.4, 22C, recombinant wild-type enzyme
1.2
Guanine
-
pH 7.4, 28C, wild-type enzyme
1.43
Guanine
-
+/-0.02, 70C
3.4
Guanine
-
pH 7.4, 22C, recombinant mutant F36G
4.3
Guanine
-
native enzyme
5
Guanine
-
recombinant enzyme
5.7
Guanine
-
wild-type enzyme
6.3
Guanine
-
pH 7.4, 22C, recombinant mutant F36K
10.5
Guanine
-
wild-type enzyme
12.1
Guanine
-
wild-type enzyme
15.8
Guanine
-
mutant enzyme
18
Guanine
-
pH 7.4, 22C, recombinant mutant F36L
20
Guanine
Q5SLS3
pH 7.9, 25C
22.1
Guanine
-
pH 7.5, 37C, recombinant mutant G69S
25.5
Guanine
-
pH 7.4, 22C, recombinant wild-type enzyme
25.5
Guanine
P20035
pH 7.4, 28C, wild-type enzyme
32.9
Guanine
-
wild-type enzyme
32.9
Guanine
-
pH 7.5, 37C, recombinant wild-type enzyme
32.9
Guanine
-
pH 7.5, 37C, recombinant enzyme
41.3
Guanine
-
wild-type enzyme
76.7
Guanine
-
wild-type, forward reaction
0.06
hypoxanthine
-
loop II-deletion mutant
0.073
hypoxanthine
-
purified recombinant chimeric enzyme DS1
0.3
hypoxanthine
-
pH 7.5, 37C, recombinant mutant L67M
0.38
hypoxanthine
-
+/-0.01, 40C
0.47
hypoxanthine
-
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.47
hypoxanthine
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.83
hypoxanthine
-
+/-0.04, 50C
0.9
hypoxanthine
-
pH 7.4, 25C, recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
0.94
hypoxanthine
-
pH 7.4, 22C, recombinant mutant L44F
1.13
hypoxanthine
-
pH 7.4, 22C, recombinant wild-type enzyme
1.13
hypoxanthine
-
pH 7.4, 28C, wild-type enzyme
1.38
hypoxanthine
-
+/-0.03, 60C
2.4
hypoxanthine
-
native enzyme
2.6
hypoxanthine
-
recombinant enzyme
2.6
hypoxanthine
-
wild-type enzyme
3.1
hypoxanthine
-
pH 7.4, 22C, recombinant mutant F36G
3.16
hypoxanthine
-
+/-0.08, 70C
3.4
hypoxanthine
-
pH 7.4, 22C, recombinant mutant F36K
3.8
hypoxanthine
-
mutant E196R
4.12
hypoxanthine
Q8R7L0
pH 7.4, 25C
5.4
hypoxanthine
-
pH 7.4, 22C, recombinant mutant F36L
5.7
hypoxanthine
-
wild-type enzyme
5.7
hypoxanthine
-
wild-type enzyme
6.2
hypoxanthine
-
mutant enzyme
6.71
hypoxanthine
-
mutant T47K
7.1
hypoxanthine
-
pH 7.4, 22C, recombinant wild-type enzyme
7.1
hypoxanthine
P20035
pH 7.4, 28C, wild-type enzyme
7.97
hypoxanthine
Q8R7L0
pH 7.4, 37C
8.5 - 9.3
hypoxanthine
-
recombinant enzyme
8.54
hypoxanthine
-
wild-type enzyme
9.1
hypoxanthine
Q5SLS3
pH 7.9, 25C
13.7
hypoxanthine
-
mutant E196Q
13.8
hypoxanthine
-
mutant E196D
15.9
hypoxanthine
Q8R7L0
pH 7.4, 50C
20.3
hypoxanthine
-
mutant E196A
22
hypoxanthine
-
pH 7.5, 37C, recombinant mutant G69S
22.9
hypoxanthine
-
wild-type enzyme
22.9
hypoxanthine
-
pH 7.5, 37C, recombinant wild-type enzyme
22.9
hypoxanthine
-
pH 7.5, 37C, recombinant enzyme
0.038
IMP
-
wild-type enzyme
0.07
IMP
-
pH 7.5, 37C, recombinant mutant L67M
0.18
IMP
-
mutant E196D
0.19
IMP
-
pH 7.5, 37C, recombinant mutant G69S
0.23
IMP
-
mutant E196A
0.46
IMP
-
pH 7.5, 37C, recombinant enzyme
0.47
IMP
-
pH 7.5, 37C, recombinant wild-type enzyme
0.51
IMP
-
mutant E196Q
0.001
inosine monophosphate
-
loop II-deletion mutant
0.23 - 0.3
inosine monophosphate
-
recombinant enzyme, reverse reaction
0.472
inosine monophosphate
-
wild-type enzyme
0.062
xanthine
-
purified recombinant chimeric enzyme DS1
0.07
xanthine
-
pH 7.4, 22C, recombinant mutant F36L
0.08
xanthine
-
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.08
xanthine
P20035
pH 7.4, 28C, recombinant chimeric mutant enzyme
0.68
xanthine
-
+/-0.04, 50C
1.2
xanthine
-
pH 7.4, 22C, recombinant mutant L44F
2.2
xanthine
-
+/-0.08, 70C
2.9
xanthine
-
pH 7.4, 22C, recombinant wild-type enzyme
2.9
xanthine
-
pH 7.4, 28C, wild-type enzyme
77
inosine monophosphate
-
wild-type enzyme
additional information
additional information
-
kinetics
-
additional information
additional information
-
wild-type and mutants: kcat for substrates hypoxanthine, guanine, xanthine, IMP, GMP, XMP, diphosphate, 5-phosphoribosyl 1-diphosphate
-
additional information
additional information
-
kcat of mutant enzymes
-
additional information
additional information
-
wild-type and diverse mutant enzymes, overview
-
additional information
additional information
-
increasing kcat with temperature (40-70C) for all substrates tested; kcat/KM for 5-phospho-alpha-D-ribose 1-diphosphate = 0.00093 mM(-1)*min(-1) at 40C, 0.00069 mM(-1)*min(-1) at 50C, 0.00357 mM(-1)*min(-1) at 60C, 0.00496 mM(-1)*min(-1) at 70C; kcat/KM for guanine = 0.00262 mM(-1)*min(-1) at 50C, 0.02631 mM(-1)*min(-1) at 70C; kcat/KM for hypoxanthine = 0.00579 mM(-1)*min(-1) at 40C, 0.00708 mM(-1)*min(-1) at 50C, 0.01719 mM(-1)*min(-1) at 60C, 0.03107 mM(-1)*min(-1) at 70C; kcat/KM for hypoxanthine similar to kcat/KM for guanine, kcat/KM for xanthine approximately 20 times lower; kcat/KM for xanthine = 0.00040 mM(-1)*min(-1) at 50C, 0.00139 mM(-1)*min(-1) at 70C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.004
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196R
158
0.02
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196A
158
0.05
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196Q
158
0.08
5-phospho-alpha-D-ribose 1-diphosphate
-
mutant E196D
158
0.1
5-phospho-alpha-D-ribose 1-diphosphate
-
wild-type enzyme
158
18
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 25C, recombinant enzyme, with guanine
158
476
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.4, 25C, recombinant enzyme, with hypoxanthine
158
0.0003
diphosphate
-
mutant E196D
17
0.002
diphosphate
-
wild-type enzyme
17
5.6
Guanine
-
pH 7.4, 25C, recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
199
0.7
hypoxanthine
-
wild-type enzyme
211
1.4
hypoxanthine
-
mutant E196R
211
2.8
hypoxanthine
-
mutant E196D
211
3.2
hypoxanthine
-
mutant E196A
211
3.8
hypoxanthine
-
mutant E196Q
211
386
hypoxanthine
-
pH 7.4, 25C, recombinant enzyme, with 5-phospho-alpha-D-ribose 1-diphosphate
211
0.0024
IMP
-
mutant E196D
232
0.016
IMP
-
wild-type enzyme
232
0.034
IMP
-
mutant E196Q
232
1
IMP
-
mutant E196A
232
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00001
(3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]propyl)phosphonic acid
-
pH 7.6, 37C
0.02
(R)-9-[2-(phosphonomethoxy)propyl]-8-bromoguanine
-
pH 7.4, 25C
0.041
(R)-9-[2-(phosphonomethoxy)propyl]-8-bromoguanine
-
pH 7.4, 25C
0.4373
(R)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
pH 8.5, 25C
0.0006
(R,S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25C
0.0059
(R,S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25C
0.015
(S)-9-[2-(phosphonomethoxy)propyl]-8-azaguanine
-
pH 7.4, 25C
0.045
(S)-9-[2-(phosphonomethoxy)propyl]-8-azaguanine
-
above, pH 7.4, 25C
0.011
(S)-9-[2-(phosphonomethoxy)propyl]-8-bromoguanine
-
pH 7.4, 25C
0.3
(S)-9-[2-(phosphonomethoxy)propyl]-8-bromoguanine
-
above, pH 7.4, 25C
0.0648
(S)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
pH 8.5, 25C
0.1823
(S)-9-[2-(phosphonomethoxy)propyl]hypoxanthine
-
pH 8.5, 25C
0.0284
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25C
0.1768
(S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25C
0.037
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, product inhibition versus IMP, substrate hypoxanthine, recombinant enzyme
0.138
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, product inhibition versus diphosphate, substrate hypoxanthine, recombinant enzyme
0.298
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, product inhibition versus diphosphate, substrate guanine, recombinant enzyme
0.423
5-phospho-alpha-D-ribose 1-diphosphate
-
pH 7.5, 37C, product inhibition versus GMP, substrate guanine, recombinant enzyme
0.5
6-methylheptyl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
above, pH 7.4, 25C
1
6-methylheptyl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
above, pH 7.4, 25C
0.0008
6-Thioguanine
-
-
0.0001
9-[2-(2-phosphonoethoxy)ethyl]guanine
-
pH 7.4, 25C
0.001
9-[2-(2-phosphonoethoxy)ethyl]guanine
-
pH 7.4, 25C
0.0003
9-[2-(2-phosphonoethoxy)ethyl]hypoxanthine
-
pH 7.4, 25C
0.0036
9-[2-(2-phosphonoethoxy)ethyl]hypoxanthine
-
pH 7.4, 25C
0.0036
9-[2-(phosphonomethoxy)-3-fluoro-propyl]guanine
-
pH 8.5, 25C
0.0227
9-[2-(phosphonomethoxy)-3-fluoro-propyl]guanine
-
pH 8.5, 25C
0.1
9-[2-(phosphonomethoxy)ethyl]-6-thioguanine
-
above, pH 7.4, 25C
1
9-[2-(phosphonomethoxy)ethyl]-6-thioguanine
-
above, pH 7.4, 25C
0.0043
9-[2-(phosphonomethoxy)ethyl]-7-deaza-8-azahypoxanthine
-
pH 7.4, 25C
0.0072
9-[2-(phosphonomethoxy)ethyl]-7-deaza-8-azahypoxanthine
-
pH 7.4, 25C
0.003
9-[2-(phosphonomethoxy)ethyl]-8-azaguanine
-
pH 7.4, 25C
0.175
9-[2-(phosphonomethoxy)ethyl]-8-azaguanine
-
pH 7.4, 25C
0.01
9-[2-(phosphonomethoxy)ethyl]-8-bromoguanine
-
pH 7.4, 25C
0.4
9-[2-(phosphonomethoxy)ethyl]-8-bromoguanine
-
above, pH 7.4, 25C
0.0016
9-[2-(phosphonomethoxy)ethyl]guanine
-
pH 7.4, 25C
0.0189
9-[2-(phosphonomethoxy)ethyl]guanine
-
pH 8.5, 25C
0.029
9-[2-(phosphonomethoxy)ethyl]guanine
-
pH 7.4, 25C
0.0559
9-[2-(phosphonomethoxy)ethyl]guanine
-
pH 8.5, 25C
0.0012
9-[2-(phosphonomethoxy)ethy]-8-hydroxyguanine
-
pH 7.4, 25C
0.068
9-[2-(phosphonomethoxy)ethy]-8-hydroxyguanine
-
pH 7.4, 25C
0.14
adenine
-
-
0.0254
ADP
-
mutant K134S, competitive versus 5-phospho-alpha-D-ribose 1-diphosphate
0.001
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25C
0.0014
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25C
0.0123
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25C
0.019
cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25C
0.008
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25C
0.0377
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25C
0.09
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 7.4, 25C
0.1151
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
-
pH 8.5, 25C
0.093
diphosphate
-
pH 7.5, 37C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate guanine, recombinant enzyme
0.122
diphosphate
-
pH 7.5, 37C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate hypoxanthine, recombinant enzyme; pH 7.5, 37C, product inhibition versus hypoxanthine, substrate hypoxanthine, recombinant enzyme
0.302
diphosphate
-
pH 7.5, 37C, product inhibition versus guanine, substrate guanine, recombinant enzyme
0.02
GMP
-
pH 7.5, 37C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate guanine, recombinant enzyme
0.1
GMP
-
pH 7.5, 37C, product inhibition versus guanine, substrate guanine, recombinant enzyme
0.004
Guanine
-
-
0.01
Guanine
-
-
0.018
Guanine
-
-
0.0058
guanine ribose 5'-phosphate
-
pH 7.4, 25C
0.01
guanine ribose 5'-phosphate
-
pH 7.4, 25C
0.023
hypoxanthine
-
-
0.08
hypoxanthine
-
-
0.0036
hypoxanthine ribose 5'-phosphate
-
pH 7.4, 25C
0.0054
hypoxanthine ribose 5'-phosphate
-
pH 7.4, 25C
0.037
IMP
-
pH 7.5, 37C, product inhibition versus 5-phospho-alpha-D-ribose 1-diphosphate, substrate hypoxanthine, recombinant enzyme
0.045
IMP
-
pH 7.4, 12 mM MgCl2, versus 5-phospho-alpha-D-ribose 1-diphosphate
0.14
propan-2-yl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
pH 7.4, 25C
0.2
propan-2-yl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
-
above, pH 7.4, 25C
0.14
xanthine
-
-
0.00000065
[(3S)-4-hydroxy-3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]butyl]phosphonic acid
-
pH 7.6, 37C
-
0.138
IMP
-
pH 7.5, 37C, product inhibition versus hypoxanthine, substrate hypoxanthine, recombinant enzyme
additional information
additional information
-
overview, inhibition constants for diverse purine nucleotides and analogues
-
additional information
additional information
-
kinetics of product inhibition in forward reaction
-
additional information
additional information
-
kinetics for product inhibition in forward and reverse reaction, wild-type enzyme
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0000021 - 0.0000072
-
purified native enzyme
0.00016
P00492
F199C mutant erythrocytes
0.0002 - 0.00029
P00492
wild-type erythrocytes
0.0008
-
wild-type MN9D cells
0.00085
-
pH 9.0, 37C, hypoxanthine phosphoribosyltransferase activity
0.0027
-
pH 9.0, 37C, guanine phosphoribosyltransferase activity
0.032
-
purified recombinant chimeric enzyme DS1, substrate guanine
0.108
-
substrate xanthine
0.147
-
purified recombinant chimeric enzyme DS1, substrate xanthine
0.226
-
purified recombinant chimeric enzyme DS1, substrate hypoxanthine
0.27
-
purified recombinant enzyme, substrate allopurinol, pH 8.0
0.28
-
substrate hypoxanthine
0.346
-
substrate guanine
0.39
-
purified enzyme, reverse reaction
0.4
-
purified recombinant enzyme, substrate guanine
0.57 - 0.76
-
recombinant enzyme, reverse reaction
0.65
-
purified enzyme
1.4
-
purified recombinant enzyme, substrate hypoxanthine, pH 8.0
1.44
-
purified recombinant enzyme, substrate hypoxanthine
1.45
-
purified recombinant enzyme, substrate hypoxanthine, in presence of 0.008 mM IMP, after 6 h
1.8
Q8R7L0
purified recombinant enzyme
3
-
about, purified enzyme
3
-
purified recombinant enzyme, substrates allopurinol and xanthine, pH 8.0
5.22
-
purified recombinant enzyme, substrate hypoxanthine, in presence of 0.038 mM IMP, after 48 h
5.4
-
purified enzyme, substrate hypoxanthine
5.4
-
purified recombinant enzyme, substrate guanine, pH 8.0
5.9
-
recombinant enzyme, substrate hypoxanthine
7.6
-
purified enzyme, substrate guanine
8.1
-
recombinant enzyme, substrate guanine
9
-
purified enzyme, brain
9.25
-
substrate hypoxanthine
11.9
-
purified recombinant enzyme, substrate hypoxanthine
13.25
-
substrate guanine
17.5
-
purified enzyme, erythrocytes
21 - 23
-
recombinant enzyme, forward reaction
25.8
-
purified recombinant enzyme, substrate guanine
27
-
purified recombinant enzyme, substrate hypoxanthine, pH 8.0
46
-
purified recombinant enzyme, substrate guanine, pH 8.0
66.5
-
purified enzyme
698.1
-
purified enzyme, method 1
705
-
purified enzyme, immunopurification
additional information
-
-
additional information
-
-
additional information
-
-
additional information
-
kinetics
additional information
-
-
additional information
-
kinetics
additional information
-
kinetics
additional information
-
kinetics in forward and reverse reaction
additional information
-
kinetics
additional information
-
-
additional information
-
kinetics in forward and reverse reaction
additional information
-
kinetic analysis and determination of catalytic efficiencies in the forward and reverse reaction for the wild-type and diverse mutant enzymes, overview
additional information
-
-
additional information
-
HPRT activity in HPRT-deficient MN9D mutant cells, overview
additional information
-
enzyme activity in erythrocyte lysate in presence or absence of Pb2+, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5
Q97W22
maximal activity with hypoxanthine and guanine
6 - 10
-
substrate hypoxanthine, broad maximum
7 - 9
-
broad maximum
7
-
2 buffer-independent pH-optima: pH 7.0 and pH 9.5
7.4 - 8.2
-
-
7.4
-
assay at
7.4
-
assay at
7.5 - 9.5
-
substrate guanine, broad maximum
7.5
-
assay at
7.5
-
assay at, forward and reverse reaction
7.5
Q97W22
maximal activity with xanthine
7.6 - 8
-
2 zones of pH-optima: pH 7.6-8.0 and pH 9.2-9.5
7.8
-
assay at
7.8
-
assay at
8.5
-
assay at
8.5
-
assay at, substrates hypoxanthine and guanine
9
-
guanine phosphoribosyltransferase activity and hypoxanthine phosphoribosyltransferase activity
9.2 - 9.5
-
2 zones of pH-optima: pH 7.6-8.0 and pH 9.2-9.5
9.5
-
2 buffer-independent pH-optima: pH 7.0 and pH 9.5
additional information
-
pI: 5.25
additional information
-
pI: 7.6
additional information
-
3 charge variant forms with pIs of 5.7, 5.5 and 5.0
additional information
-
3 charge variant forms with pIs of 6.2, 6.4 and 6.6
additional information
-
3 charge variant forms with pIs of 5.6, 5.7 and 5.9
additional information
-
pI: 4.4
additional information
-
-
additional information
-
3 charge variant forms with pIs of 5.6, 5.85, 5.9
additional information
-
3 charge variant forms with pIs of 5.6, 5.7 and 5.9
additional information
-
pI of 4.8 for the hypoxanthine specific enzyme, pI of 5.5 for the guanine specific enzyme
additional information
-
3 charge variant forms: pIs of 6.75, 5.3, 5.2
additional information
Q9NJI5
recombinant enzyme, pI: 8.2
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.3 - 9.7
-
pH 6.3: about 50% of activity maximum, pH 9.7: about 75% of activity maximum
7 - 8.5
-
pH 7.0: about 80% of activity maximum, pH 8.5: about 70% of activity maximum
7.5 - 10
-
half-maximal activity at pH 7.5, and 10.0, guanine phosphoribosyltransferase activity
7.5 - 9.5
-
half-maximal activity at pH 7.5, and 9.5, hypoxanthine phosphoribosyltransferase activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
-
assay at room temperature
22
-
assay at room temperature
28
-
assay at
28
P20035
assay at
30
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at
37
-
assay at, forward and reverse reaction
37
-
assay at
37
-
assay at
38
-
assay at
additional information
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
a neuroblastoma cell line
Manually annotated by BRENDA team
-
amelanotic human melanoma cell, hypoxanthine phosphoribosyltransferase-negative
Manually annotated by BRENDA team
-
of a mentally retarded child and its family members, partial enzyme deficiency
Manually annotated by BRENDA team
-
myeloid leukemic cell line
Manually annotated by BRENDA team
-
a T-ALL cell line
Manually annotated by BRENDA team
-
from peripheral blood
Manually annotated by BRENDA team
-
G0 peripheral blood lymphocytes
Manually annotated by BRENDA team
-
dopaminergic
Manually annotated by BRENDA team
Giardia intestinalis Portland
-
-
-
Manually annotated by BRENDA team
-
tissue culture cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
isozyme HXGPRT-I lacking the 49-amino acid insertion
Manually annotated by BRENDA team
-
a fuel-metabolizing microbody unique to this parasite, exclusively
Manually annotated by BRENDA team
-
isozyme HXGPRT-II possessisng the 49-amino acid insertion, localizes to the inner membrane complex (IMC) of the parasite
Manually annotated by BRENDA team
Escherichia coli K12, Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
-
-
-
Manually annotated by BRENDA team
Escherichia coli K12, Salmonella enterica subsp. enterica serovar Typhimurium LT-2
-
-
-
Manually annotated by BRENDA team
additional information
-
the mutant enzyme, lacking the targeting signal, is located throughout the parasite, including subcellular organelles such as nucleus and flagellum
-
Manually annotated by BRENDA team
additional information
-
differential localization of alternatively spliced isozymes, overview
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Brachybacterium faecium (strain ATCC 43885 / DSM 4810 / NCIB 9860)
Caldanaerobacter subterraneus subsp. tengcongensis (strain DSM 15242 / JCM 11007 / NBRC 100824 / MB4)
Caldanaerobacter subterraneus subsp. tengcongensis (strain DSM 15242 / JCM 11007 / NBRC 100824 / MB4)
Caldanaerobacter subterraneus subsp. tengcongensis (strain DSM 15242 / JCM 11007 / NBRC 100824 / MB4)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Leptospira interrogans serogroup Icterohaemorrhagiae serovar copenhageni (strain Fiocruz L1-130)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
Shewanella pealeana (strain ATCC 700345 / ANG-SQ1)
Staphylococcus aureus (strain USA300 / TCH1516)
Staphylococcus aureus (strain USA300 / TCH1516)
Sulfolobus solfataricus (strain 98/2)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Trypanosoma cruzi (strain CL Brener)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42000
-
gel filtration in presence of MgCl2
638161
45000
Q97W22
gel filtration
724940
48000
-
gel filtration in absence of MgCl2
638161
50000
Q9NJI5
recombinant enzyme, gel filtration
638420
51000
-
gel filtration
638394
54500 - 54800
-
equilibrium sedimentation analysis, gel filtration
638401
58000 - 63000
-
gel filtration, isokinetic sucrose density gradient centrifugation
638403
66000
-
gel filtration
638162
68000
-
gel filtration
638396
71000
-
-
638160
72000
-
brain enzyme, gel filtration
638395
78000 - 85000
-
gel filtration
638390, 638397
79000
-
-
638388
80000 - 85000
-
gel filtration, acrylamide gel electrophoresis
638390
80000
-
gel filtration
638398
81000 - 83000
-
sedimentation equilibrium centrifugation
638390, 638399
85000
-
gel filtration
638392
85000
-
sedimentation equilibrium method
638405
87400
Q8R7L0
recombinant enzyme, gel filtration
663292
100000
-
3 charge variant forms, native gradient gel electrophoresis
638389
103000
-
dynamic light scattering
685403
103100
-
gel filtration chromatography
685403
105000
-
pore gradient electrophoresis
638402
150000
-
gel filtration
638393
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 26000, SDS-PAGE
?
-
x * 26000, SDS-PAGE
?
-
x * 24000, SDS-PAGE
?
-
x * 24352-24353, recombinant mutant enzymes, mass spectroscopy and DNA sequence determination
?
-
x * 41000-45000, sedimentation equilibrium in presence of guanidine-HCl
?
-
x * 25000-27000, SDS-PAGE
dimer
-
-
dimer
-
2 * 64000, SDS-PAGE
dimer
-
2 * 29000, SDS-PAGE
dimer
Q9NJI5
2 * 23000, recombinant enzyme, SDS-PAGE
dimer
-
2 * 29500, SDS-PAGE
dimer
-
2 * 26229-26232, in presence of KCl, SDS-PAGE, mass spectroscopy and DNA sequence determination
dimer
-
2 * 34000-34700, SDS-PAGE
dimer
P00492
residues 198-204 are involved in the largest dimer interface
dimer
Q97W22
2 * 20600, SDS-PAGE
dimer
Giardia intestinalis Portland
-
2 * 29000, SDS-PAGE
-
dimer
-
2 * 20600, SDS-PAGE
-
homohexamer
-
dynamic light scattering (pH 7.5, 25 C) and gel filtration chromatography (HR 10/30 Superdex 200, FPLC, pH 7.5)
monomer
-
1 * 51000, SDS-PAGE
monomer or dimer
-
the recombinant chimeric enzyme exists as a mixture of monomeric and dimeric protein in solution, but shifts to a tetramer on addition of phosphoribosyl diphosphate
octamer
-
8 * 18000, SDS-PAGE
tetramer
Q26997
-
tetramer
-
4 * 26000, SDS-PAGE
tetramer
-
4 * 24000, SDS-PAGE
tetramer
-
4 * 26229-26232, in absence of KCl, SDS-PAGE, mass spectroscopy and DNA sequence determination
tetramer
-
4 * 19000, SDS-PAGE
tetramer
Q8R7L0
4 * 22800, SDS-PAGE
tetramer
-
active enzyme form, subunit A composition, overview
tetramer
-
the recombinant chimeric enzyme exists as a mixture of monomeric and dimeric protein in solution, but shifts to a tetramer on addition of phosphoribosyl diphosphate
tetramer
P20035
the recombinant chimeric enzyme exists as a mixture of monomeric and dimeric protein in solution, but shifts to a tetramer on addition of phosphoribosyl diphosphate
trimer
-
3 * 27000, SDS-PAGE
trimer
-
3 * 26000, SDS-PAGE
trimer
-
3 * 25000, SDS-PAGE
monomer or dimer
P20035
the recombinant chimeric enzyme exists as a mixture of monomeric and dimeric protein in solution, but shifts to a tetramer on addition of phosphoribosyl diphosphate
additional information
-
stereoview of the three-dimensional structure of subunit, subunit interaction
additional information
-
structure determination and analysis
additional information
-
Pro93 and Tyr197 form part of crucial interactions holding together the AB interface in the unliganded or GMP-bound forms of HGPRT, while Pro93 and His26 interact at the interface after binding of phosphoribosyl diphosphate
additional information
P20035
Pro93 and Tyr197 form part of crucial interactions holding together the AB interface in the unliganded or GMP-bound forms of HGPRT, while Pro93 and His26 interact at the interface after binding of phosphoribosyl diphosphate
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
no glycoprotein
-
no carbohydrate
no glycoprotein
-
no glucosamine, sialic acid and hexose
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
free enzyme or enzyme complexed with IMP, hanging drop vapour diffusion method, 20C, 10 mg/ml protein in 20 Tris-HCl, pH 7.4, mixed with a molar excess of IMP, 0.001 ml protein solution mixed with equal volume of reservoir solution containing 0.2 M magnesium acetate tetrahydrate, 0.1 M sodium cacodylate, pH 6.5, 12% w/v PEG 4000, or protein solution with 1 mM IMP mixed with reservoir solution containing 15% PEG 8000, 0.1 M sodium cacodylate, pH 6.5, 0.2 M magnesium acetate tetrahydrate, X-ray diffraction structure determination and analysis at 2.2-2.5 A resolution
-
purified recombinant mutant L160I enzyme, hanging drop vapour diffusion method, 0.001 ml of 10 mg/ml protein in 20 mM Tris-HCl, pH 7.4, excess GMP in a molar ratio 4:1, is mixed with equal volume of crystallization solution containing 0.2 M CaCl2 dihydrate, 0.1 M HEPES, pH 7.5, 28% PEG 400, 20C, 2 weeks, X-ray diffraction structure determination and analysis at 1.7 A resolution, purified recombinant wild-type enzyme, hanging drop vapour diffusion method, 0.001 ml of 10 mg/ml protein in 20 mM Tris-HCl, pH 7.4, excess IMP in a molar ratio 4:1, is mixed with equal volume of crystallization solution containing 0.2 M magnesium acetate tetrahydrate, 0.1 M sodium cacodylate, pH 6.5, 12% PEG 4000, 20C, within 1 week, X-ray diffraction structure determination and analysis at 2.2 A resolution
-
enzyme in complex with 2-(phosphonoethoxy)ethyl guanine, 2-(phosphonoethoxy)ethyl hypoxanthine, and (R,S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine, hanging drop vapor diffusion method, mixing of equal volumes of well solution, containing 0.1 M citrate pH 5.5, 10% isopropyl alcohol and 29% PEG 4000, and protein inhibitor complex with 17 mg/ml prtoein, and 3.3 mM for 2-(phosphonoethoxy)ethyl guanine, 3.9 mM (R,S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine, and 3.0 mM for 2-(phosphonoethoxy)ethyl hypoxanthine, X-ray diffraction structure determination and analysis at 2.6-2.78 A resolution
-
purified recombinant mutant C22A/C105A/C205A enzyme 1. free or 2. in complex with inactive purine base analogue 7-hydroxy [4,3d] pyrazolo pyrimidine and 5-phospho-alpha-D-ribose 1-diphosphate, or 3. complexed with IMP or GMP, or 4. complexed with transition state analogue immuncillinHP-Mg2+-diphosphate, hanging drop vapour diffusion method, 18 mg/ml protein in 0.05 M Tris-HCl, pH 7.4, 1 mM MgCl2, 1 mM DTT, mixing of 0.002 ml of both protein and reservoir solution, the latter containing 0.2 M ammonium acetate, 0.1 m sodium acetate, pH 4.6, 30% w/v PEG 4000, 17C, 2-7 days, cryoprotection by 30% glycerol in reservoir solution, X-ray diffraction structure determination and analysis at 1.9 A resolution
-
recombinant chimeric mutant enzyme complex with the product GMP, 12 mg/ml protein and 5 mM GMP in 0.1 M Tris, pH 8.0, and 2.0 M ammonium sulfate, 2-5 days, X-ray diffraction structure determination and analysis at 2.8 A resolution, modeling
-
spectral analysis of the crystal structure of the HGPRT/immucillin-G 5'-phosphate/diphosphate complex
-
ultraviolet resonance Raman spectroscopy study on the complexes of enzyme with products IMP, GMP, and XMP, both in Homo sapiens and Plasmodium falciparum, in resonance with the purine nucleobase electronic absorption. Human hypoxanthine guanine phosphoribosyltransferase catalyzes the phosphoribosylation of guanine and hypoxanthine, while the Plasmodium falciparum enzyme acts on xanthine as well. Spectra of bound nucleotides show that the enzyme distorts the structure of the nucleotides. The distorted structure resembles that of the deprotonated nucleotide. The two proteins assemble similar active sites for their common substrates. While the human enzyme does not bind XMP, Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferase perturbs the pKa of bound XMP
-
recombinant enzyme, 7 mg/ml, hanging-drop vapour-diffusion method, TMD buffer, pH 7.5, + equal volume of reservoir solution: 18C or 4C, pH 5.6 , 19% isopropanol, 19% polyethylene glycol 4000, 5% glycerol, or 17% polyethylene glycol 4000, 5% glycerol
Q9NJI5
recombinant chimeric mutant enzyme complex with the product GMP, 12 mg/ml protein and 5 mM GMP in 0.1 M Tris, pH 8.0, and 2.0 M ammonium sulfate, 2-5 days, X-ray diffraction structure determination and analysis at 2.8 A resolution, modeling
P20035
ultraviolet resonance Raman spectroscopy study on the complexes of enzyme with products IMP, GMP, and XMP, both in Homo sapiens and Plasmodium falciparum, in resonance with the purine nucleobase electronic absorption. Human hypoxanthine guanine phosphoribosyltransferase catalyzes the phosphoribosylation of guanine and hypoxanthine, while the Plasmodium falciparum enzyme acts on xanthine as well. Spectra of bound nucleotides show that the enzyme distorts the structure of the nucleotides. The distorted structure resembles that of the deprotonated nucleotide. The two proteins assemble similar active sites for their common substrates. While the human enzyme does not bind XMP, Plasmodium falciparum hypoxanthine guanine phosphoribosyltransferase perturbs the pKa of bound XMP
-
structure in the unliganded form, in complex with IMP and in complex with GMP, to 2.1, 1.9 and 2.2 A resolution, respectively. The overall fold of the IMP complex is similar to that of the unliganded form, but the main-chain and side-chain atoms of the active site move to accommodate IMP. The overall folds of the IMP and GMP complexes are almost identical to each other. Enzyme belongs to group I
Q5SLS3
crystallization in complex with GMP and IMP, structure analysis
-
mutant enzyme D150A, crystallization complexed with xanthosine 5'-monophosphate, diphosphate and 2 Mg2+, post transition state structure analysis, active site structure
-
the recombinant enzyme is complexed with Mg2+, 5-phosphoribosyl 1-diphosphate and inactive substrate analogue 9-deazaguanine, hanging drop method, enzyme complex, 20 mg/ml, is precipitated by 0.1 M Tris-HCl, pH 8.0, 30% polyethylene glycol 4000, 0.2 M Li2SO4, 0.5% beta-octylglucoside at 4C, X-ray diffraction structure analysis
-
analysis of crystal structure
-
crystallization and X-ray structure determination and analysis, 1 molecule of GMP bound per dimer
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.2
-
10 min, 50% loss of activity
638400
7 - 9.3
-
10 min, stable
638400
11
-
10 min, 50% loss of activity
638400
additional information
-
preincubation for 10 min at pH 5.0 or pH 10.5 prior to enzyme assay at pH 8.5 does no affect the enzyme activity
638394
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
-
pH 7.4, stable
638393
40
-
pH 7.4, gradual decrease of activity
638393
50
Q8R7L0
half-life: 75 min, irreversible inactivation
663292
60 - 65
-
stable
638358
60
-
1.5 mM GMP, 10 min, complete loss of activity
638161
60
-
mutant and wild-type enzyme, 8 min, stable
638421
60
-
3 h, wild-type and mutant F36L, over 80% remaining activity
660798
70
-
0.5 h, wild-type and mutant F36L, over 80% remaining activity
660798
85
-
if first incubated in 1 mM 5-phospho-alpha-D-ribose 1-diphosphate, remarkably stable
638390
85
-
half-life: 3 min
638392
85
-
if first incubated in 1 mM 5-phospho-alpha-D-ribose 1-diphosphate, remarkably stable
638397
additional information
-
-
638400
additional information
-
-
661691
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
5-phospho-alpha-D-ribose 1-diphosphate stabilizes
-
glycerol or sucrose or dimethylsulfoxide stabilizes the purified enzyme at -70C
-
activation by substrate and product IMP destabilizes the enzyme, the unactivated ligand-free enzyme is more stable
-
DTT and hypoxanthine stabilize
-
5-phospho-alpha-D-ribose 1-diphosphate stabilizes
-
5-phospho-alpha-D-ribose 1-diphosphate stabilizes against heat inactivation
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
frozen, partially purified enzyme, 4 months without loss of activity
-
4C, purified recombinant enzyme at 0.5 mg/ml, 100 mM Tris-HCl, pH 7.4, 12 mM MgCl2, 3 months, no loss of activity
Q8R7L0
-20C, dilute aqueous purified enzyme preparation, a few weeks
-
-80C, mutant and wild-type enzyme, stable up to 3 years
-
0C, 10 mM phosphate, pH 7.1, 1 mM DTT, 10 mM Mg2+, 2 h, no loss of activity
-
-70C, wild-type enzyme and mutants, except mutant S95C, stable up to 6 months
-
4C, freshly purified enzyme, 10 mM phosphate, pH 6.8, 10 mM DTT, 1 mM 5-phosphoribosyl 1-diphosphate, rapid loss of 90% activity within 48 h
-
5C, purified enzyme, 10 mM phosphate, pH 6.8, 1 mM DTT, 0.2 mM 5-phosphoribosyl 1-diphosphate, 0.06 hypoxanthine, loss of 7% activity after 4-8 weeks
-
-20C, several months
-
-20C, dilute aqueous purified enzyme preparation, a few weeks
-
-20C, purified enzyme, 6 mM 5-phospho-alpha-D-ribose 1-diphosphate, 2 mM MgCl2, stable for at least a month
-
4C, 50 mM Tris-HCl, pH 7.8, 1 M KCl, 10 mM MgCl2, stable at least 1 month
-
4C, 50 mM Tris-HCl, pH 7.8, complete loss of activity after 4 days
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
-
recombinant enzyme from Escherichia coli, 16fold to homogeneity by ion exchange and adsorption chromatography, and gel filtration
Q8R7L0
recombinant wild-type enzyme and His-tagged mutant L160I enzyme from Escherichia coli, wild-type enzyme to homogeneity by ion exchange and adsorption chromatography, and gel filtration, mutant in a multistep procedure, overview
-
from brain and liver
-
2 methods
-
recombinant wild-type enzyme and mutants from Escherichia coli
-
2 methods
-
3 isoenzymes
-
from erythrocytes and from brain
-
recombinant chimeric mutant enzyme from Escherichia coli strain Su609 by anion exchange chromatography
-
recombinant enzyme
-
recombinant from Escherichia coli
-
recombinant wild-type and mutants F36L, F36G, F36K from Escherichia coli
-
recombinant from Escherichia coli
-
recombinant wild-type and mutant from Escherichia coli
-
recombinant from Escherichia coli
Q9NJI5
recombinant enzyme from Escherichia coli strain BL21 (DE3) 1-2fold to homogeneity by anion exchange chromatography, gel filtration, and hydrophobic interaction chromatography
-
native enzyme by anion exchange and cation exchange chromatographies and affinity chromatography on immobilized Reactive Red 120, method development, overview, recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant chimeric mutant enzyme from Escherichia coli strain Su609 by anion exchange chromatography
P20035
recombinant from Escherichia coli , large scale
-
recombinant wild-type and mutant L44F from Escherichia coli
-
recombinant wild-type and mutant L44F from Escherichia coli, the enzyme shows very low activity
-
thermal treatment (1 h, 70C), immobilized metal affinity chromatography with Hi-Trap nickel chelating column (pH 7.5, elution with 200 mM imidazole), cleavage of His-tag with thrombin followed by second IMAC
-
recombinant enzyme
-
recombinant from Escherichia coli
-
recombinant wild-type enzyme and mutant/s from Escherichia coli
-
recombinant wild-type and mutant enzymes from Escherichia coli by GMP affinity and cation exchange chromatography
-
recombinant wild-type and mutant enzymes from Escherichia coli strain DH5alpha by GMP affinity chromatography
-
recombinant wild-type enzyme and loop II-deletion mutant from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21(DE3) as soluble protein
Q8R7L0
expression of wild-type and mutant L160I enzymes in Escherichia coli strain BL21(DE3)
-
functional overexpression of wild-type enzyme and expression of mutants in Escherichia coli
-
expressed in Escherichia coli strain BL21(DE3); gene HGPRT, expression in Escherichia coli strain BL21(DE3)
-
expressed in MN-9D cells; functional expression of the HPRT enzyme from a minigene encoding human HPRT driven by the chicken beta-actin promoter in enzyme-deficient MN9D cell lines, which restores HPRT activity and reverses the engrailed transcription factor, En1 and En2, overexpression of the mutant
-
expression in Escherichia coli
-
expression of wild-type and chimeric enzymes in enzyme-deficient Escherichia coli strain, complementation study; overexpression in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli, functional complementation study
-
gene HPRT, determination of the mutagenic potential of succinyl-acetone by determining the frequencies of somatic mutations in the HPRT reporter gene, overview
-
gene HPRT, DNA and amino acid sequence determination
-
gene HPRT, DNA sequence determination, expression analysis under different radiation conditions, overview
-
gene hprt, sequencing of wild-type and mutant enzymes
P00492
gene HPRT1
-
HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in vivo T-cell clonal lineages, overview, establishing of HPRT mutant mass cultures
-
overexpression in Escherichia coli
-
overexpression of the chimeric mutant enzyme in Escherichia coli strain Su609
-
wild-type and mutant enzymes from lymphocytes treated or not treated with myosmine
-
functional expression of wild-type enzyme and mutants in an enzyme-deficient Escherichia coli strain
-
DNA and amino acid sequence determination and analysis, functional expression in Escherichia coli BL21(DE3)
Q9NJI5
HGPRT, DNA and amino acid sequence determination and analysis, expression in Escherichia coli strain BL21 (DE3)
-
expression as His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
expression in Escherichia coli
-
expression of wild-type and chimeric enzymes in enzyme-deficient Escherichia coli strain, complementation study, overexpression of chimeric mutant DS1
-
expression of wild-type and mutant enzyme in Escherichia coli, complementation of an enzyme-deficient Escherichia coli strain by the wild-type and mutant L44F at growth temperatures 20C and 37C, and at 42C only by the wild-type enzyme
-
expression of wild-type and mutant enzyme in Escherichia coli, functional complementation study
-
overexpression in an enzyme-deficient Escherichia coli strain
-
overexpression of the chimeric mutant enzyme in Escherichia coli strain Su609
P20035
from genomic DNA in pGEM-T-Eeasy, in pET15b for expression with hexa-His tag in Escherichia coli B21 Star (DE3)
-
DNA sequence determination, expression in Escherichia coli
-
mouse neuroblastoma hypoxanthine-guanine phosphoribosyltransferase cDNA clone
-
expressed in Escherichia coli
Q97W22
gene HXGPRT, two isozymes, genetic organization, expression analysis of two alternative-splicing-derived isozymes, which differ in the presence or absence of a 49-amino acid insertion, specified by a single differentially spliced exon, but exhibit similar temporal expression patterns, isozyme expression in parasites lacking the endogenous hxgprt gene, expression of isozyme I in the cytosol and of isozyme II inthe inner membrane complex in enzyme-deficient parasites, co-expression of both isoforms results in the formation of heterooligomers, which distribute between the cytosol and IMC
-
functional expression in Escherichia coli
-
functional expression of wild-type and mutant T47K in an enzyme-deficient Escherichia coli strain
-
functional expression of wild-type enzyme and mutants in an enzyme-deficient Escherichia coli strain
-
expression of active wild-type and of mutant enzymes in Escherichia coli strain DH5alpha
-
expression of wild-type and mutant enzymes in Escherichia coli
-
functional expression of wild-type and loop II-deletion mutant in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
mutational HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype, and causes Lesch-Nyhan disease pathogenesis, microarray analysis of HPRT-deficient MN9D cells, phenotype, e.g. with increases in the mRNAs for engrailed 1 and 2, En1 and En2, transcription factors, overview. Restoration of HPRT reverses engrailed overexpression in MN9D cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A72G
-
site-directed mutagenesis, exchange in diphosphate binding site, decreased Km-value for diphosphate and guanine, increased Km-value for 5-phosphoribosyl 1-diphosphate, reduced activity
G71A
-
site-directed mutagenesis, no activity
G71E
-
site-directed mutagenesis, no activity
G71R
-
site-directed mutagenesis, no activity
T70K
-
site-directed mutagenesis, exchange in diphosphate binding site, 6.7fold lower Km-value for diphosphate, lower Km for guanine, 2fold increase in Km-value for 5-phosphoribosyl 1-diphosphate, reduced activity
T70K/A72G
-
site-directed mutagenesis, exchange in diphosphate binding site, decreased Km-value for diphosphate and guanine, increased Km-value for 5-phosphoribosyl 1-diphosphate, reduced activity
A192V
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
A64P
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
C105A
-
prepared via splicing by overlap extension, reduced oxidation ofthe enzyme during storage
C205A
-
prepared via splicing by overlap extension, reduced oxidation ofthe enzyme during storage
C22A
-
prepared via splicing by overlap extension, reduced oxidation ofthe enzyme during storage
C22A/C105A/C205A
-
site-directed mutagenesis, kinetic and physical properties are similar to the wild-type enzyme, but the mutant enzyme is more resistant to oxidation
C22A/C105A/C205A
-
site-directed mutagenesis, the exchanges stabilize the enzyme protein, but kinetic and structural properties of the mutant enzyme are identical to wild-type human HGPRT
C23F
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
D185G
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
D31E
-
identification of another genetic variation within the gout-affected population in Taiwan with mutation on exon 2 with T to G transition at cDNA base 93 resulting in a change from aspartic acid to glutamic acid at position 31
D44V
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
E196A
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196D
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196Q
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196R
-
site-directed mutagenesis, the mutant shows increased activity compared to the wild-type enzyme
E196V
-
a naturally occuring mutation that leads to the Lesch-Nyhan syndrome
F199C
P00492
a naturally occuring mutation T596G, leads to 8% residual HPRT activity and causes juvenile-onset, severe gouty arthritis, nephrolithiasis, and mild neurologic symptoms. Adenine phosphoribosyltransferase, APRT, EC 2.4.2.7, in erythrocytes from subjects with HPRT deficiency is typically increased about 23fold compared with controls. Modeling of the mutated protein for prediction of the mechanisms of partial enzymatic activity
F36A
-
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
F36E
-
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
F36G
-
site-directed mutagenesis, inactive mutant
F36K
-
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
F36L
-
random mutagenesis, mutant phosphoribosylates xanthine, mutant does not bind the purine substrate directly, long-range modulation via loop IV influence the substrate specificity, altered enzyme stability
F36L
-
wild-type human enzyme does not accept xanthine as substrate, mutant F36L does catalyze the conversion of xanthine to XMP with a kcat much lower than those of hypoxanthine and guanine and fails to perturb the pKa of XMP
F36W
-
site-directed mutagenesis, unaltered substrate specificity compared to the wild-type enzyme
G140D
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
G70E
-
naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
G70E
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
G70R
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
H204X
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
H60R
-
naturally occuring mutation of HPRT1 gene, causes no altered phenotype compared to the wild-type enzyme
I137T
-
DNA sequence determination and identification of the naturally occurring point mutation in the conserved 5-phosphoribosyl-1-diphosphate binding motif, causing a variant of Lesch-Nyhan syndrome, the mutation affects the affinity of the enzyme for 5-phosphoribosyl-1-diphosphate through structural alterations
I9S
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
K159E
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
K68A
-
conformational changes, shifted catalytic loop closer to the active site
L147F
-
natural occuring point mutation leading to enzyme deficiency, which is not correlated with a physiological syndrome
L147P
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
L65P
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
L68P
-
naturally occuring mutation in an Argentine individual, the patient shows the LND phenotype, determination of the altered urine purine alkaloid metabolite contents
L68R
-
naturally occuring mutation in an Argentine individual, the patient shows the LND phenotype, determination of the altered urine purine alkaloid metabolite contents
L78Q
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
P24R
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
P25T
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
Q144X
-
naturally occuring nonsense mutation of HPRT1 gene, exchange of 430C-T, causes the Lesch-Nyhan syndrome
R48H
-
naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
R51X
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
S162R
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
T124P
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
T139P
-
naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
V158G
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
V188A
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
Y195C
-
naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
Y195C
-
naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
Y195S
-
naturally occuring mutation in an Argentine individual, the patient shows the HRND phenotype, determination of the altered urine purine alkaloid metabolite contents
S95A
-
site-directed mutagenesis, dramatic reduction of catalytic activity, weak complementation of bacterial enzyme deficient strain
S95C
-
site-directed mutagenesis, 2-3fold reduction of kcat, weak complementation of bacterial enzyme deficient strain
S95E
-
site-directed mutagenesis, dramatic reduction of catalytic activity, no complementation of bacterial enzyme deficient strain
S95T
-
site-directed mutagenesis, 2-3fold reduction of kcat, complementation of bacterial enzyme deficient strain
Y96F
-
site-directed mutagenesis, dramatic reduction of catalytic activity, no complementation of bacterial enzyme deficient strain, 4-5fold decrease of Km value for 5-phosphoribosyl 1-diphosphate
L44F
-
site-directed mutagenesis, mutant does not phosphoribosylate guanine and xanthine, modulation via loop IV influence the substrate specificity, altered enzyme stability
D163E
-
site directed mutagenesis, slightly changed substrate affinities compared to wild-type
D163N
-
site-directed mutagensis, exchange of xanthine binding residue, loss of the binding ability and activity against xanthine and XMP
F162L
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site directed mutagenesis, no effect on purine base specificity
I104G
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site directed mutagenesis, increased Km values for hypoxanthine, guanine, and xanthine
K134Q
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site directed mutagenesis, mutant recognizes adenine as substrate in addition, but less efficient than mutant K134S
K134S
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site directed mutagenesis, mutant recognizes adenine as substrate in addition, increased Km values for hypoxanthine, guanine, and xanthine
R155E
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site directed mutagenesis, reduced affinity to GMP and XMP, catalysation of the forward reaction with guanine and xanthine at accelerated rates, 15fold increased Km for xanthine
R155K
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site directed mutagenesis, reduced affinity to GMP and XMP, catalysation of the forward reaction with guanine and xanthine at accelerated rates, insensitive to phenylglyoxal
T47K
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site-directed mutagenesis, exchange of diphosphate binding site residue, 4-10fold decreased Km for diphosphate compared to the wild-type
Y156F
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site directed mutagenesis, weakened binding of GMP and XMP
Y156W
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site directed mutagenesis, slightly changed substrate affinities compared to wild-type
G69S
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reduced activity compared to the wild-type enzyme
L160I
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site-directed mutagenesis, crystal structure determination
additional information
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random enzyme mutations induced by neutron irradiation of CHO cells, analysis of the molecular structure of the HPRT mutations and the types of point mutations using direct sequencing of PCR fragments , overview
M54L
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naturally occuring mutation of HPRT1 gene, causes the Lesch-Nyhan syndrome
additional information
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additional information
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construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes, altered substrate specificities
additional information
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determination of the frequency of HPRT deficiency within the gout-affected population in Taiwan, overview
additional information
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induction of HPRT mutations in G0 peripheral blood lymphocytes exposed in vitro to gamma rays at low, 0.0014 Gy/min, and high, 0.85 Gy/min, dose rates, the mutation increases at both high and low radiation rates, dose-rate effect on the induced HPRT mutant frequency correlating inversely with the cell curvival, overview
additional information
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construction of a chimera of Plasmodium falciparum and human HGPRTs, which consists of the core of the protein from the human enzyme and the hood region from the parasite enzyme. Replacement of Tyr197 of human HGPRT by Ile207 in the chimera disrupts the interaction at the AB interface in the absence of PRPP. In the presence of PRPP, the interaction between Pro93 and His26 can restore the AB interface, shifting the chimeric enzyme to a tetrameric state, active site structure, overview
additional information
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genotyping for mutations in the HPRT gene in healthy individuals and Lesch-Nyhan syndrome patients in Japanese population, diverse deletion mutations, detailed overview
additional information
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myosmine exhibits small, but significant, mutagenic potential and causes HPRT mutagenesis in nonsmoker lymphocytes, mutation frequency, overview
additional information
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shRNA knockdown of HPRT gene expression leading toloss of 94% activity, HPRT-deficient NT2 cells demonstrate aberrant expression of several transcription factors and dopaminergic markers
Y72C
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naturally occuring mutation of HPRT1 gene, causes HPRT-related hyperuricemia
additional information
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wild-type enzyme complements enzyme deficiency of the bacterial enzyme in Escherichia coli
additional information
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construction of mutant lacking the Ser-Lys-Val C-terminal targeting signal, mutant enzyme is located throughout the parasite, including subcellular organelles such as nucleus and flagellum
Y96V
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site-directed mutagenesis, dramatic reduction of catalytic activity, no complementation of bacterial enzyme deficient strain, 4-5fold decrease of Km value for 5-phosphoribosyl 1-diphosphate
additional information
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generation of HPRT gene knock-out mice, the mutant mice show 55% increased expression of the serotonin receptor 2C, HTR2C, semiquantitative realtime RT-PCR expression analysis
L44F
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site-directed mutagenesis, temperature-sensitive mutant, no complementation of an enzyme-deficient Escherichia coli strain at 42C, only at 20C and 37C
additional information
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construction of 4 chimeric enzymes with segments of human and Plasmodium falciparum enzymes, altered substrate specificities
additional information
P20035
construction of a chimera of Plasmodium falciparum and human HGPRTs, which consists of the core of the protein from the human enzyme and the hood region from the parasite enzyme. Replacement of Tyr197 of human HGPRT by Ile207 in the chimera disrupts the interaction at the AB interface in the absence of PRPP. In the presence of PRPP, the interaction between Pro93 and His26 can restore the AB interface, shifting the chimeric enzyme to a tetrameric state, active site structure, overview
D150A
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reduced activity compared to wild-type, kcat for hypoxanthine, guanine, and xanthine are reduced by 11fold, 296fold, and 8.6fold, respectively, Km value for alpha-D-5-phosphoribosyl 1-diphosphate is reduced by 6.5fold
additional information
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chimeric constructs expressing N-terminal peptides of 11 amino acids from isoform I or of 60 amino acids from isoform II fused to a chloramphenicol acetyl transferase reporter show that the N-terminal domain of isoform II is both necessary and sufficient for membrane association
L67M
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highly reduced activity with hypoxanthine compared to the wild-type enzyme, mutant is not active with guanine
additional information
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construction of deletion mutant lacking 7 amino acid residues, Y82-S88, of the active site loop II, resulting in highly reduced kcat-values and in increased Km-values for the substrates
additional information
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saturation mutagenesis and complement selection for investigation of functional roles of residues Leu67 and Gly69, sequencing of 70 clones and identification of 30 different mutations, several mutants of L67 or G69 support bacterial growth on minimal medium, but only L67M and G69S can be expressed and purified from overexpressing bacteria, overview
additional information
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saturation mutagenesis for randomly exchange of amino acids of the active site loop II, construction of diverse mutants of the residues S102 to Q112, kinetic analysis and determination of catalytic efficiencies in the forward and reverse reaction, overview
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
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the branched bi-enzyme system with xanthine oxidase is an important biochemical system to evaluate the efficiency of the anticancer drug 6-mercaptopurine, overview
medicine
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potential target for antiparasitic chemotherapy
medicine
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prospective pharmacodynamic study to determine the effect of combination therapy for treatment of inflammatory bowel disease on the activity of hypoxanthine-guanine phosphoribosyltransferase, which activates of thiopurine prodrugs to thioguanine nucleotides. The activity of hypoxanthine-guanine phosphoribosyltransferase and thioguanine nucleotides concentrations was measured in red blood cells during thiopurine monotherapy and after 4 weeks of combination therapy. The activity of hypoxanthine-guanine phosphoribosyltransferase was also measured after 12 weeks of combination therapy. Combination therapy increases the activity of hypoxanthine-guanine phosphoribosyltransferase and subsequently thioguanine nucleotides concentrations
molecular biology
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HPRT mutations in vivo in human T-lymphocytes are useful probes for mechanistic investigations, molecular analyses of isolated mutants reveal their underlying mutational changes as well as the T-cell receptor gene rearrangements present in the cells in question, overview
molecular biology
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the HPRT gene is used as reporter gene in HL-60 cells for investigation of the mutagenic potential of succinyl-acetone by determining the frequencies of somatic mutations in the HPRT reporter gene, overview
medicine
Q9NJI5
potential target for antiparasitic chemotherapy
drug development
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the enzyme is a target for antimalarial inhibitor design and development
medicine
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potential target for antiparasitic chemotherapy
medicine
-
potential target for antiparasitic chemotherapy
medicine
-
potential target for antiparasitic chemotherapy
medicine
-
target for antiparasite drug design
medicine
-
target for anti-trichomonial therapy
medicine
-
potential target for antiparasitic chemotherapy
pharmacology
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enzyme is a potential drug target in the treatment of parasite caused disease
pharmacology
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the enzyme is a target for mechanism-based design of specific inhibitors