Aminoimidazole ribonucleotide

The l5N NMR spectra has been recorded for 5-aminoimidazole ribonucleotide (180 R1 =/3-D-Ribofuranosyl R2 = H). The NH2 group was observed at a chemical shift of 8-354.5 (nitromethane as internal standard) (90JA4891). 

AIR. /-(S-O-Phosphono-d-D-ribofuranosyl)-lH-imidazol-5-amine 5-amino-I-ribofuranosylimidazole S -phosphate 5-aminoimidazole ribonucleotide 5-aminoimida-zole ribotide 5 -amino -1 -(5 -phosphofuranoribosy] )imida -zole. C H14N307P mol wt 295-19. C 32.55%. H 4.78%, N 14.23%, O 37.94%, P 10.49%. An intermediate in the biosynthesis of purines. Synthesis from formylglycinamide ribonucleotide Levenberg, Buchanan, J. Biol Chem. 224, 1005 (1957) Lukens, Buchanan, ibid. 234, 1791 (1959). 

Phosphoribosyl-1-pyrophosphate synthetase 2 aminophosphoribosyltransferase 3 phospho-ribosylglycinamide synthetase 4 glycinamide ribonucleotide transformylase 5 iV-formylglycin-amidine ribonucleotide amidoligase 6 5-aminoimidazole ribonucleotide synthetase 7 5-amino-imidazole ribonucleotide carboxylase 8 5-aminoimidazole-4-iV-succinocarboxamide ribonucleotide synthetase 9 adenylosuccinate lyase 10 5-aminoimidazole-4-carboxamide ribonucleotide transformylase 11 inosinicase... 

Thiamine monophosphate is built from 2-methyl-4-amino-5-hydroxymethyl pyrimidine pyrophosphate and 4-methyl-5-(j8-hydroxyethyl)-thiazole (Fig. 183). The pyrimidine part is derived from 5-aminoimidazole ribonucleotide, an intermediate of purine biosythesis (D 10.4). As yet the origin of C-5 and the CH2OH-group as well as that of the CHg-group is stiU unknown. The thiazole moiety is derived from the precursors given in Fig. 184. Intermediates were not identified. 

Biotin was implicated in purine bio thesis by the observations that (a) the fixation of CO2 was markedly lowered in the tissue nucleic acids of biotin-deficient rats S7), and (b) 5-aminoimidazole ribonucleotide accumulated in biotin-deficient yeast 1S8,1S9). In the latter instance, the addition of aspartic acid to the deficient yeast suppressed the accumulation of the arylamine. Since biotin was thought to be involved in aspartic acid biosynthesis (140, 141), it is likely that the synthesis of this amino acid was limiting in biotin deficiency and that the ect of the deficiency on purine biosynthesis was indirect 142),... 

One of the steps in the biosynthesis of a nucleotide called inosine monophosphate is the formation of aminoimidazole ribonucleotide from formyjglycin-amidine ribonucleotide. Propose a mechanism. 

Aimi,J., Qiu, H., Williams, J., Zalkin, H., and Dixon, J. E. (1990). De novo purine nucleotide biosynthesis cloning of human and avian cDNAs encoding the trifunctional glycinam-ide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. colt. Nucleic Acids Res., 18, 6665-6672. 

E.J. Mueller, S. Oh, E. Kavalerchik, T.J. Kappock, E. Meyer, C. Li, S.E. Ealick, and J. Stubbe. 1999. Investigation of the ATP binding site of Escherichia coli aminoimidazole ribonucleotide synthetase using affinity labeling and site-directed mutagenesis Biochemistry 38 9831-9839. (PubMed)... 

This chemistry seems less probable, however, given the structural similarity of the smPurL proteinand aminoimidazole ribonucleotide (AIR) synthetase (PurM), another enzyme in the purine biosynthetic pathway that is known to form an iminophosphate intermediate (Scheme 16). Under in vitro conditions, FGAR-AT can use ammonia as an alternate nitrogen source when glutamine is absent. 

Synthetic efforts were also directed towards the development of novel enzyme inhibitors, in particular that of aminoimidazole ribonucleotide... 

The conversion of FGAM to aminoimidazole ribonucleotide (AIR) is catalyzed by the aminoimidazole ribotide synthase, PurM. In this reaction the five-membered ring of the purine base is formed the formyl oxygen is activated by the y-phosphate of the ATP for the nucleophilic attack by N-1 of FGAR, resulting in ring closure [240]. In bacteria, PurM is encoded separately, and in mammals it is part of a trifunctional enzyme, which includes PurD and PurN [241]. 

Aminoimidazole ribonucleotide (AIR) Aminoimidazolecarboxylate ribonucleotide (CAIR) Aminoimidazole succinocarboxamide ribonucleotide (SAICAR) Aminoimidazolecarboxamide ribonucleotide (AICAR) Formamidoimidazolecarboxamide ribonucleotide (FAICAR)... 

Aminoimidazole-4-Carboxamide Ribonucleotide Transformylase Carbonic Anhydrase II DNA Gyrase... 

Aminoimidazole-4-carboxamide ribonucleotide (AlCAR) transformylase inhibitor, Ki = 154 nM, IC50 = 600 nM... 

Li C, Xu L, Wolan DW, Wilson lA, Olson AJ. Virtual screening of human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase against the NCI diversity set by use of AutoDock to identify novel nonfolate inhibitors. J Med Chem 2004 47 6681-90. 

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