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Phosphoribosylglycinamide formyltransferase (, ''2-amino-N-ribosylacetamide 5'-phosphate transformylase'', ''GAR formyltransferase'', ''GAR transformylase'', ''glycinamide ribonucleotide transformylase'', ''GAR TFase'', ''5,10-methenyltetrahydrofolate:2-amino-N-ribosylacetamide ribonucleotide transformylase'') is an enzyme with system name ''10-formyltetrahydrofolate:5'-phosphoribosylglycinamide N-formyltransferase''. This enzyme catalyses the following chemical reaction :10-formyltetrahydrofolate + N1-(5-phospho-D-ribosyl)glycinamide tetrahydrofolate + N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide This THF dependent enzyme catalyzes a nucleophilic acyl substitution of the formyl group from 10-formyltetrahydrofolate (fTHF) to N1-(5-phospho-D-ribosyl)glycinamide (GAR) to form N2-formyl-N1-(5-phospho-D-ribosyl)glycinamide (fGAR) as shown above.〔McMurry, J. and Tadhg, B. The Organic Chemistry of Biological Pathways〕 This reaction plays an important role in the formation of purine through the ''de novo'' purine biosynthesis pathway. This pathway creates inosine monophosphate (IMP), a precursor to adenosine monophosphate (AMP) and guanosine monophosphate (GMP). AMP is a building block for important energy carriers such as ATP, NAD+ and FAD, and signaling molecules such as cAMP. GARTfase's role in ''de novo'' purine biosynthesis makes it a target for anti-cancer drugs and its overexpression during postnatal development has been connected to Down syndrome. There are two known types of genes encoding GAR transformylase in E.coli: purN and purT, while only purN is found in humans. Many residues in the active site are conserved across bacterial, yeast, avian and human enzymes.〔 == Enzyme Structure == In humans, GARTfase is part of trifunctional enzyme which also includes glycinamide ribnucleotide synthase (GARS) and aminoimidazole ribonucleotide synthetase (AIRS). This protein (110kDa) catalyzes steps 2, 3 and 5 of de novo purine biosynthesis. The proximity of these enzyme units and flexibility of the protein serves to increase pathway throughput. GARTfase is located on the C-terminal end of the protein. Human GARTfase has been crystallized by vapor-diffusion sitting drop method and imaged at the Stanford Synchrotron Radiation Laboratory (SSRL) by at least two groups.〔 The structure can be described by two subdomains which are connected by a seven-stranded beta sheet. The N- terminal domain consists of a Rossman type mononucleotide fold, with a four strand part of the beta sheet surrounded on each side by two alpha helices. The beta sheet continues into the C terminal domain, where on one side it is covered by a long alpha helix and on the other it is partially exposed to solvent. It is the cleft between the two subdomains where the active site lies. The cleft consists of the GAR binding site and the folate binding pocket. The folate binding pocket is delineated by pteridine-binding cleft, the formyl transfer region and the benzoylglutamate region which bind thepteridine head and a benzoylglutamate tail connected by a formyl bound nitrogen of fTHF. This folate binding region has been the subject of much research because its inhibition by small molecules has led to the discovery of antineoplastic drugs. The folate binding loop has been shown to change conformation depending on the pH of solution and as such Human GAR transformylase shows highest activity around pH 7.5-8. Lower pH (~4.2) conditions change the conformation of the substrate (GAR) binding loops as well.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Phosphoribosylglycinamide formyltransferase」の詳細全文を読む スポンサード リンク
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