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- Name help_outline 10-formyldihydrofolate Identifier CHEBI:57452 Charge -2 Formula C20H19N7O7 InChIKeyhelp_outline UXFQDXABPXWSTK-ZDUSSCGKSA-L SMILEShelp_outline [H]C(=O)N(CC1=Nc2c(NC1)nc(N)[nH]c2=O)c1ccc(cc1)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 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-D-ribosyl)imidazole-4-thiocarboxamide Identifier CHEBI:145873 Charge -2 Formula C9H13N4O7PS InChIKeyhelp_outline ICVRYQWTGDCSSQ-UUOKFMHZSA-L SMILEShelp_outline N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP([O-])(=O)[O-])C(=C(C(N)=S)N=C1)N 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 6-thio-IMP Identifier CHEBI:145875 Charge -2 Formula C10H11N4O7PS InChIKeyhelp_outline ZKRFOXLVOKTUTA-KQYNXXCUSA-L SMILEShelp_outline O1[C@@H]([C@H]([C@H]([C@@H]1N2C=NC3=C2N=CNC3=S)O)O)COP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 7,8-dihydrofolate Identifier CHEBI:57451 Charge -2 Formula C19H19N7O6 InChIKeyhelp_outline OZRNSSUDZOLUSN-LBPRGKRZSA-L SMILEShelp_outline Nc1nc2NCC(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 8 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:62676 | RHEA:62677 | RHEA:62678 | RHEA:62679 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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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.