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 hide
2.4.2.8
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RECOMMENDED NAME
GeneOntology No.
hypoxanthine phosphoribosyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
IMP + diphosphate = hypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pentosyl group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenine and adenosine salvage III
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adenine salvage
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Biosynthesis of secondary metabolites
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Drug metabolism - other enzymes
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guanine and guanosine salvage
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guanine and guanosine salvage II
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Metabolic pathways
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Purine metabolism
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purine metabolism
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SYSTEMATIC NAME
IUBMB Comments
IMP:diphosphate phospho-D-ribosyltransferase
Guanine and 6-mercaptopurine can replace hypoxanthine.
CAS REGISTRY NUMBER
COMMENTARY hide
9016-12-0
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
in MDCK cells
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Manually annotated by BRENDA team
strain K12
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
strain Portland I, 3 charge variant forms
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
gene hgprt
SwissProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
Northern elephant seal
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Manually annotated by BRENDA team
hyperthermophile
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Manually annotated by BRENDA team
phosphoribosyltransferases for hypoxanthine and guanine are separate enzymes; strain LT-2
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
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-
-
-
?
2-hydroxy-6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
2-hydroxy-6-mercaptopurine ribotide + diphosphate
show the reaction diagram
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-
-
-
?
3-hydroxy-2-pyrazinecarboxamide + 5-phospho-alpha-D-ribose 1-diphosphate
3-oxo-4-(5-O-phosphono-beta-D-ribofuranosyl)-3,4-dihydropyrazine-2-carboxamide + diphosphate
show the reaction diagram
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T-1105, poor substrate
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-
?
3-hydroxy-2-pyrazinecarboxamide + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
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T-1105, poor substrate
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-
?
6-fluoro-3-hydroxy-2-pyrazinecarboxamide + 5-phospho-alpha-D-ribose 1-diphosphate
6-fluoro-3-oxo-4-(5-O-phosphono-beta-D-ribofuranosyl)-3,4-dihydropyrazine-2-carboxamide + diphosphate
show the reaction diagram
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T-705, poor substrate
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-
?
6-fluoro-3-hydroxy-2-pyrazinecarboxamide + 5-phospho-alpha-D-ribose 1-diphosphate
? + diphosphate
show the reaction diagram
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T-705, poor substrate
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-
?
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-thioinosine monophosphate + diphosphate
show the reaction diagram
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-
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?
6-mercaptopurine + 5-phospho-alpha-D-ribose 1-diphosphate
thioinosinic monophosphate + diphosphate
show the reaction diagram
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a thiopurine antimetabolite
a therapeutically active metabolite
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6-thioguanine + 5-phospho-alpha-D-ribose 1-diphosphate
6-thio-GMP + diphosphate
show the reaction diagram
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-
-
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?
8-azahypoxanthine + 5-phospho-alpha-D-ribose 1-diphosphate
8-aza-IMP + diphosphate
show the reaction diagram
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-
-
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?
allopurinol + 5-phospho-alpha-D-ribose 1-diphosphate
allopurinol ribonucleoside 5'-monophosphate + diphosphate
show the reaction diagram
GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
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
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-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
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
XMP + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
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r
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GMP + diphosphate
guanine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
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
IMP + diphosphate
hypoxanthine + 5-phospho-alpha-D-ribose 1-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
xanthosine 5'-phosphate + diphosphate
show the reaction diagram
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
XMP + diphosphate
show the reaction diagram
XMP + diphosphate
xanthine + 5-phospho-alpha-D-ribose 1-diphosphate
show the reaction diagram
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r
additional information
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
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activates, can replace Mg2+, Km: 0.066-0.075 mM
additional information
-
no activation by Ca2+
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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-hydroxy-2-[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]methyl]propyl)phosphonic acid
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(3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]propyl)phosphonic acid
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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
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(R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-8-bromoguanine
(R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
(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
2-Amino-6-mercaptopurine
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competitive to hypoxanthine
3-((7-hydroxy-1H-pyrazolo[4,3-d]pyrimidin-3-yl)methylamino)propylphosphonate
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4-(2-methyl-4-oxo-(3H) quinazolin-3-yl)-benzoic acid (4-formyl-benzylidene) hydrazide
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78.12% inhibition at 0.25 mg/ml
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4-(2-methyl-6,8-dibromo-4-oxo-(3H)quinazolin-3-yl)-benzoic acid (4-formyl-benzylidene) hydrazide
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79.07% inhibition at 0.25 mg/ml
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4-(2-methyl-6-bromo-4-oxo-(3H) quinazolin-3-yl)-benzoic acid (4-formyl-benzylidene) hydrazide
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77.06% inhibition at 0.25 mg/ml
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4-(2-phenyl-4-oxo-(3H) quinazolin-3-yl)-benzoic acid (4-formyl-benzylidene) hydrazide
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79.42% inhibition at 0.25 mg/ml
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4-(2-phenyl-6,8-dibromo-4-oxo-(3H)quinazolin-3-yl)-benzoic acid (4-formyl-benzylidene) hydrazide
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79.71% inhibition at 0.25 mg/ml
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4-(2-phenyl-6-bromo-4-oxo-(3H) quinazolin-3-yl)-benzoic acid (4-formyl-benzylidene) hydrazide
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79.55% inhibition at 0.25 mg/ml
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5-phospho-alpha-D-ribose 1-diphosphate
6-aminopurine nucleotides
6-Chloropurine
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6-Hydroxypurine nucleotides
6-Mercaptopurine
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competitive to hypoxanthine
6-methylheptyl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
6-Thioguanine
6-thioinosine
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9-beta-Arabinofuranosylhypoxanthine
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9-deazaguanine
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uncompetitive inhibitor
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
9-[2-(phosphonomethoxy)ethy]-8-hydroxyguanine
acyclic nucleoside phosphonates
adenine
Azaguanine
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cyclic (R)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
cyclic (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine
diethyl dicarbonate
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alkylation of Arg155, complete inactivation at pH 9.0, pH dependent
diphosphate
guanine
guanine ribose 5'-phosphate
hypoxanthine
hypoxanthine ribose 5'-phosphate
immucillin-G 5'-phosphate
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active site contacts in the HGPRT/immucillin-G 5'-phosphate/diphosphate complex, overview
immucillin-H
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transition state analogue, binds tightly to the active site, inhibition mechanism and kinetics
immucillin-H 5'-phosphate
Inosine
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slight inhibition
Isoniazid
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99% inhibition at 0.25 mg/ml
Mg2+
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inhibitory effects are noncompetitive against 5-phosphoribose 1-diphosphate
nucleotides
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p-chloromercuribenzoate
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reversed by dithiothreitol or 2-mercaptoethanol
Phenylglyoxal
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irreversible, complete inactivation, alkylation of Arg155, GMP protects, no alkylation of mutant R155K
ppGpp
propan-2-yl hydrogen {[2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)ethoxy]methyl}phosphonate
purine nucleotides
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rifampicin
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99% inhibition at 0.25 mg/ml
Tetranitromethane
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complete inactivation at pH 9.0, pH dependent, modifies Tyr96 in the active site
xanthine
[(+/-)-2(R/S)-3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propoxy]phosphonic acid
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[(+/-)-2(R/S)-[([2-chloro-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
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[(2R)-2-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
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[(2R)-3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propoxy]phosphonic acid
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[(2S)-2-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-3-hydroxypropoxy]phosphonic acid
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[(2S,3R)-2,4-dihydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butoxy]phosphonic acid
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[(3R)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
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[(3S)-1,1-difluoro-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
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[(3S)-3-[([2-amino-4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-1,1-difluoro-4-hydroxybutyl]phosphonic acid
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[(3S)-4-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
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[(3S)-4-hydroxy-3-[[(4-oxo-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidin-7-yl)methyl]amino]butyl]phosphonic acid
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competitive. 592fold lower affinity for human enzyme
[2-hydroxy-3-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propyl] phosphonic acid
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[2-[(2-[4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]ethyl)amino]ethyl]phosphonic acid
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[2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]ethoxy]phosphonic acid
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[3-hydroxy-2-[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]-2-(hydroxymethyl)propoxy]phosphonic acid
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[3-[(2-[4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]ethyl)amino]propyl]phosphonic acid
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[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]butyl]phosphonic acid
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[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]ethyl]phosphonic acid
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[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]methyl]phosphonic acid
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[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]pentyl]phosphonic acid
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[[([4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl]methyl)amino]propyl]phosphonic acid
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
acetate
GMP
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0.05 mM, at least 2fold stimulation, hypoxanthine phosphoribosyltransferase activity
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.069
3-hydroxy-2-pyrazinecarboxamide
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at pH 7.4 and 37C
-
0.001 - 2.039
5-phospho-alpha-D-ribose 1-diphosphate
0.035 - 0.138
5-phosphoribosyl 1-diphosphate
6.426
6-fluoro-3-hydroxy-2-pyrazinecarboxamide
-
at pH 7.4 and 37C
-
0.0062
6-Mercaptopurine
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-
0.0076
6-Thioguanine
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-
0.36
8-Azahypoxanthine
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-
0.0346
adenine
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mutant K134S
0.0117 - 0.135
allopurinol
0.0039 - 0.968
diphosphate
0.0225 - 0.029
GMP
0.001 - 0.5
guanine
0.00052 - 0.126
hypoxanthine
0.0016 - 1.043
IMP
0.0054 - 0.09
inosine monophosphate
0.036 - 0.853
xanthine
additional information
additional information
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