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Human aminoimidazole ribonucleotide synthetase, AIRS domain

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PDB Code 2V9Y Target Class Nucleotide metabolism Target GART Alias AIRS, GARS, GART, GARTF, MGC47764, PAIS, PGFT, PRGS Disease Area/Function cancer Date Deposited Aug 28 2007 Authors Welin, M., Lehtio, L., Arrowsmith, C.H., Berglund, H., Busam, R., Collins, R., Dahlgren, L.G., Herman, M.D., Edwards, A., Flodin, S., Flores, A., Graslund, S., Hammarstrom, M., Hallberg, B.M., Holmberg-Schiavone, L., Johansson, I., Kallas, A., Karlberg, T., Kotenyova, T., Moche, M., Nyman, T., Persson, C., Sagemark, J., Stenmark, P., Sundstrom, M., Thorsell, A.G., Tresaugues, L., van den Berg, S., Weigelt, J., Nordlund, P. Related Structure 2QK4

About this structure

Human GART is a trifunctional enzyme, compositing glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS) and glycinamide ribonucleotide transformylase (GART). This enzyme is carrying out three steps in the de novo synthesis of purines. The second domain, AIRS or PurM of the human GART is carrying out the fifth step in the de novo synthesis of purines. AIRS is catalysing the conversion of formylglycinamidine ribonucleotide (FGAM) and ATP to make aminoimidazole ribonucleotide (AIR), ADP and Pi. Being an enzyme in the core nucleotide metabolism makes GART a potential target for anti-cancer therapeutic drugs [1].

The structure of human AIRS domain was solved with molecular replacement using the E.coli structure (pdb-code:1cli) to a resolution of 2.1 Å. The AIRS structure forms a dimer similar to the E.coli AIRS structure. There are no substrates bound in the E.coli structure but a sulfate ion is suggested to bind to the FGAM binding domain. In the human AIRS structure there is a sulfate ion found in a similar position as for the E.coli structure [2].

References

  1. Adam, T. (2005) Purine de novo synthesis – mechanism and clinical implications Klin. Biochem. Metab. 13:177-181.
  2. Li C, Kappock TJ, Stubbe J, Weaver TM, Ealick SE. X-ray crystal structure of aminoimidazole ribonucleotide synthetase (PurM), from the Escherichia coli purine biosynthetic pathway at 2.5 A resolution. Structure. 1999 Sep 15;7(9):1155-66.