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- Name help_outline (6R)-10-formyltetrahydrofolate Identifier CHEBI:195366 Charge -2 Formula C20H21N7O7 InChIKeyhelp_outline AUFGTPPARQZWDO-YPMHNXCESA-L SMILEShelp_outline [H]C(=O)N(C[C@H]1CNC2=C(N1)C(=O)NC(N)=N2)C1=CC=C(C=C1)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 10 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 5-amino-1-(5-phospho-β-D-ribosyl)imidazole-4-carboxamide Identifier CHEBI:58475 (Beilstein: 6669264) help_outline Charge -2 Formula C9H13N4O8P InChIKeyhelp_outline NOTGFIUVDGNKRI-UUOKFMHZSA-L SMILEShelp_outline NC(=O)c1ncn([C@@H]2O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]2O)c1N 2D coordinates Mol file for the small molecule Search links Involved in 11 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 5-formamido-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide Identifier CHEBI:58467 Charge -2 Formula C10H13N4O9P InChIKeyhelp_outline ABCOOORLYAOBOZ-KQYNXXCUSA-L SMILEShelp_outline [H]C(=O)Nc1c(ncn1[C@@H]1O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]1O)C(N)=O 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (6S)-5,6,7,8-tetrahydrofolate Identifier CHEBI:57453 (Beilstein: 10223255) help_outline Charge -2 Formula C19H21N7O6 InChIKeyhelp_outline MSTNYGQPCMXVAQ-RYUDHWBXSA-L SMILEShelp_outline Nc1nc2NC[C@H](CNc3ccc(cc3)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)Nc2c(=O)[nH]1 2D coordinates Mol file for the small molecule Search links Involved in 41 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:22192 | RHEA:22193 | RHEA:22194 | RHEA:22195 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping.
Rayl E.A., Moroson B.A., Beardsley G.P.
We report here the cloning and sequencing of the cDNA, purification, steady state kinetic analysis, and truncation mapping studies of the human 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICARFT/IMPCHase). These steps of de novo purine biosynthesis, respect ... >> More
We report here the cloning and sequencing of the cDNA, purification, steady state kinetic analysis, and truncation mapping studies of the human 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICARFT/IMPCHase). These steps of de novo purine biosynthesis, respectively. In all species of both prokaryotes and eukaryotes studied, these two activities are present on a single bifunctional polypeptide encoded on the purH gene. The human purH cDNA is 1776 base pairs in length encoding for a 591-amino acid polypeptic (Mr = 64,425). The human and avian purH cDNAs are 75 and 81% similar on the nucleotide and amino acid sequence level, respectively. The Km values for AICAR and (6R,6S)10-formyltetrahydrofolate are 16.8 microM +/- 1.5 and 60.2 microM +/-5.0, respectively, for the cloned, purified human enzyme. A 10-amino acid sequence within the COOH-terminal portion of human AICARFT/IMPCHase has some degree of homology to a previously noted "folate binding site." Site directed mutagenesis studies indicate that this sequence plays no role in enzymatic activity. We have constructed truncation mutants which demonstrate that each of the two enzyme activities can be expressed independent of the other. IMPCHase and AICARFT activities are located within the NH2-terminal 223 and COOH-terminal 406 amino acids, respectively. The truncation mutant possessing AICARFT activity displays steady state kinetic parameters identical to those of the holoenzyme. << Less
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Biosynthesis of the purines. XXVI. The identification of the formyl donors of the transformylation reactions.
HARTMAN S.C., BUCHANAN J.M.
J Biol Chem 234:1812-1816(1959) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Human AICAR transformylase: role of the 4-carboxamide of AICAR in binding and catalysis.
Wall M., Shim J.H., Benkovic S.J.
We have prepared 4-substituted analogues of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to investigate the specificity and mechanism of AICAR transformylase (AICAR Tfase). Of the nine analogues of AICAR studied, only one analogue, 5-aminoimidazole-4-thiocarboxamide ribonucleotide, was a ... >> More
We have prepared 4-substituted analogues of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) to investigate the specificity and mechanism of AICAR transformylase (AICAR Tfase). Of the nine analogues of AICAR studied, only one analogue, 5-aminoimidazole-4-thiocarboxamide ribonucleotide, was a substrate, and it was converted to 6-mercaptopurine ribonucleotide. The other analogues either did not bind or were competitive inhibitors, the most potent being 5-amino-4-nitroimidazole ribonucleotide with a K(i) of 0.7 +/-0.5 microM. The results show that the 4-carboxamide of AICAR is essential for catalysis, and it is proposed to assist in mediating proton transfer, catalyzing the reaction by trapping of the addition compound. AICAR analogues where the nitrogen of the 4-carboxamide was derivatized with a methyl or an allylic group did not bind AICAR Tfase, as determined by pre-steady-state burst kinetics; however, these compounds were potent inhibitors of IMP cyclohydrolase (IMP CHase), a second activity of the bifunctional mammalian enzyme (K(i) = 0.05 +/-0.02 microM for 4-N-allyl-AlCAR). It is proposed that the conformation of the carboxamide moiety required for binding to AICAR Tfase is different than the conformation required for binding to IMP CHase, which is supported by inhibition studies of purine ribonucleotides. It is shown that 5-formyl-AICAR (FAICAR) is a product inhibitor of AICAR Tfase with K(i) of 0.4 +/-0.1 microM. We have determined the equilibrium constant of the transformylase reaction to be 0.024 +/-0.001, showing that the reaction strongly favors AICAR and the 10-formyl-folate cofactor. The coupling of the AICAR Tfase and IMP CHase activities on a single polypeptide allows the overall conversion of AICAR to IMP to be favorable by coupling the unfavorable formation of FAICAR with the highly favorable cyclization reaction. The current kinetic studies have also indicated that the release of FAICAR is the rate-limiting step, under steady-state conditions, in the bifunctional enzyme and channeling is not observed between AICAR Tfase and IMP CHase. << Less
Biochemistry 39:11303-11311(2000) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.