Information on EC 6.3.2.6 - phosphoribosylaminoimidazolesuccinocarboxamide synthase

New: Word Map on EC 6.3.2.6
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY hide
6.3.2.6
-
RECOMMENDED NAME
GeneOntology No.
phosphoribosylaminoimidazolesuccinocarboxamide synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate = ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
-
-
-
-
carboxylic acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
inosine-5'-phosphate biosynthesis I
-
-
inosine-5'-phosphate biosynthesis II
-
-
inosine-5'-phosphate biosynthesis III
-
-
Metabolic pathways
-
-
purine metabolism
-
-
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate:L-aspartate ligase (ADP-forming)
Forms part of the purine biosynthesis pathway.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-67-0
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
bifunctional enzyme with phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase activities
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Pigeon
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 1-(5'-phosphoribosyl)-5-amino-4-carboxyimidazole + L-Asp
?
show the reaction diagram
ATP + 1-(5'-phosphoribosyl)-5-amino-4-carboxyimidazole + L-Asp
ADP + phosphate + 1-(5'-phosphoribosyl)-5-amino-4-(N-succinocarboxamide)-imidazole
show the reaction diagram
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
ADP + phosphate + (S)-2-[5-amino1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
additional information
?
-
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
ATP + 1-(5'-phosphoribosyl)-5-amino-4-carboxyimidazole + L-Asp
?
show the reaction diagram
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
ADP + phosphate + (S)-2-[5-amino1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
-
can replace Mg2+, maximal activation at 0.04 mM
Mn2+
-
can replace Mg2+, maximal activation at 0.06 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
adenosine 5'-(beta,gamma-imido)triphosphate
-
-
IMP
-
competitive with respect to 1-(5'-phosphoribosyl)-5-amino-4-carboxyimidazole
Maleate
-
competitive with respect to L-Asp
PCMB
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.3
1-(5'-phosphoribosyl)-5-amino-4-carboxyimidazole
-
-
0.036
Asp
-
-
0.04
MgATP2-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.26 - 4
adenosine 5'-(beta,gamma-imido)triphosphate
7 - 13
IMP
12 - 50
Maleate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
11.06
-
-
additional information
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
-
enzyme is expressed in rapidly dividing tissues
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Clostridium perfringens (strain ATCC 13124 / DSM 756 / JCM 1290 / NCIMB 6125 / NCTC 8237 / Type A)
Ehrlichia chaffeensis (strain ATCC CRL-10679 / Arkansas)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Geobacillus kaustophilus (strain HTA426)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440)
Mycobacterium abscessus (strain ATCC 19977 / DSM 44196 / CIP 104536 / JCM 13569 / NCTC 13031 / TMC 1543)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
76000
-
ultracentrifugation
96000
-
gradient gel electrophoresis of the native protein
350000
-
gel filtration
360000
-
gel filtration
420000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
structure overview
octamer
oligomer
-
x * 50000, SDS-PAGE
trimer
-
3 * 27000, SDS-PAGE
additional information
-
structure modeling, overview
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapor diffusion, crystal structures of the ADP and the ADP/4-carboxy-5-aminoimidazole ribonucleotide complexes of SAICAR synthetase. ADP and 4-carboxy-5-aminoimidazole ribonucleotide bind to the active site in association with three Mg2+, two of which coordinate the same oxygen atom of the 4-carboxyl group of CAIR, whereas, the third coordinates the alpha- and beta-phosphoryl groups of ADP. The polypeptide fold for residues 204-221 of the Escherichia coli structure differs significantly from those of the ligand-free SAICAR synthetase from Thermatoga maritima and the adenine nucleotide complexes of the synthetase from Saccharomyces cerevisiae
the 2.8 A resolution structure reveals that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homo-octamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains
-
co-crystallization of SAICAR synthetase from Pyrococcus horikoshii with substrates and other nucleotides produces eight ligand bound structures, five in C2221 and three in H3 space groups. These ligand bound complexes have minor structural deviations compared to their corresponding apo structures. In most of the structures the hydrolyzed product of the nucleotide triphosphates are bound to the enzyme
-
space group P31, presence of a hexamer in the asymmetric unit
at 2.5 A resolution
-
crystals of SAICAR complexed with 5'-phosphoribosyl-5-amino-4-imidazolecarboxamide and succinic acid are grown by hanging drop vapor diffusion at room temperature, mother liquor consists of 24 mg/ml SAICAR, 1 M ammonium sulfate, 100 mM 5'-phosphoribosyl-5-amino-4-imidazolecarboxamide, 100 mM succinic acid and 50 mM Tris-HCl, pH 7.5, crystals diffract to 1.3 A
-
hanging drop vapor diffusion, drops contain protein at a concentration of 8-15 mg/ml in 50 mM Tris-HCl, pH 7.0, 40 mM aspartic acid and 1.0-1.25 M ammonium sulfate, crystals diffract to 1.9 A resolution
-
hanging-drop vapor-diffusion method. Crystals of the complex of the enzyme SAICAR synthase with the reaction product belong to space group P2(1)2(1)2(1) containing one molecule per asymmetric unit
-
to 2.8 A resolution, space group P2
-
hanging-drop vapor-diffusion conditions, 2.2 A resolution crystal structure. Protein structure is described and compared with that of the ATP-SAICAR synthase complex from yeast
-
purified enzyme in 150 mM NaCl, 1 mM DTT, 10 mM HEPES-KOH, pH 7.5, is mixed with 50 mM Tris pH 8.0, 2M ammonium sulfate and 1% PEG400, X-ray diffraction structure determination and analysis at 2.8 A resolution, modeling
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4 - 8
-
narrow stability profile with maximal stability at pH 7.6
1266
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
DTT is essential in maintaining the stability, in absence of DTT the activity is completely lost within two hours of extraction
-
the ionic strength required to maintain enzyme activity is 0.1 M Tris HCl, at pH 7.8
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, concentrated enzyme, above 1 mg/ml, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, DEAE-Sephadex, Butyl-Toyopearl
-
copurification of EC 4.1.1.21/EC 6.3.2.6
-
copurification of the bifunctional protein complex possessing phosphoribosylaminoimidazole carboxylase (EC 4.1.1.21) and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (EC 6.3.2.6)
-
partial
Pigeon
-
recombinant His-tagged enzyme from insect HighFive cells by nickel affinity and anion exchange chromatography, followed by gel filtration
-
recombinant protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
bifunctional enzyme 5-aminoimidazole ribonucleotide carboxylase/5-aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase
-
cloned in a high-copy-number plasmid
-
cloning of a 12-gene cluster encoding 9 enzymes for de novo purine nucleotide synthesis
-
expression in Escherichia coli
functional complementation of Escherichia coli purC purine auxotroph
overexpression in Escherichia coli
-
recombinant expression of His-tagged enzyme in insect HighFive cells
-
SAICAR synthetase is cloned into a lambdaPL expression vector to give plasmid pJS408, overexpression
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities. It is an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway
Show AA Sequence (10360 entries)
Longer loading times are possible. Please use the Sequence Search for a certain query.