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Gene Review

GUA1  -  GMP synthase (glutamine-hydrolyzing)

Saccharomyces cerevisiae S288c

Synonyms: GMP synthetase, Glutamine amidotransferase, YM8261.11, YMR217W
 
 
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Disease relevance of GUA1

 

High impact information on GUA1

  • Only this first step of GDP synthesis pathway is regulated, since the latter steps, encoded by the GUA1 and GUK1 genes, are guanine-insensitive [2].
  • IGP synthase is a glutamine amidotransferase that incorporates ammonia derived from glutamine into the unusual nucleotide, N(1)-[(5'-phosphoribulosyl)-formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR) to form 5'-(5-aminoimidazole-4-carboxamide) ribonucleotide (AICAR) and imidazole glycerol phosphate (IGP) [3].
  • The enzyme is also a glutamine amidotransferase, which produces ammonia in a glutaminase active site and channels it through a 30-A internal tunnel to a cyclase active site [4].
  • Acivicin [(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid] was investigated as an inhibitor of the triad glutamine amidotransferases, IGP synthase and GMP synthetase [5].
  • The data indicate that acivicin undergoes a glutamine amidotransferase mechanism-based covalent bond formation in the presence of nucleotide substrates or products [5].
 

Biological context of GUA1

  • A comparison of the amino acid sequences of CP A1 polypeptide with the glutamine amidotransferase domains of anthranilate and p-amino-benzoate synthetases from various sources has revealed the presence in each of these sequences of three highly conserved regions of 8, 11 and 6 amino acids respectively [6].
 

Associations of GUA1 with chemical compounds

 

Regulatory relationships of GUA1

 

Other interactions of GUA1

References

  1. Cloning and sequencing of the GMP synthetase-encoding gene of Saccharomyces cerevisiae. Dujardin, G., Kermorgant, M., Slonimski, P.P., Boucherie, H. Gene (1994) [Pubmed]
  2. Transcriptional regulation of the yeast gmp synthesis pathway by its end products. Escobar-Henriques, M., Daignan-Fornier, B. J. Biol. Chem. (2001) [Pubmed]
  3. Substrate-induced changes in the ammonia channel for imidazole glycerol phosphate synthase. Myers, R.S., Jensen, J.R., Deras, I.L., Smith, J.L., Davisson, V.J. Biochemistry (2003) [Pubmed]
  4. Toward understanding the mechanism of the complex cyclization reaction catalyzed by imidazole glycerolphosphate synthase: crystal structures of a ternary complex and the free enzyme. Chaudhuri, B.N., Lange, S.C., Myers, R.S., Davisson, V.J., Smith, J.L. Biochemistry (2003) [Pubmed]
  5. Mechanism for acivicin inactivation of triad glutamine amidotransferases. Chittur, S.V., Klem, T.J., Shafer, C.M., Davisson, V.J. Biochemistry (2001) [Pubmed]
  6. Nucleotide sequence of yeast gene CP A1 encoding the small subunit of arginine-pathway carbamoyl-phosphate synthetase. Homology of the deduced amino acid sequence to other glutamine amidotransferases. Werner, M., Feller, A., Piérard, A. Eur. J. Biochem. (1985) [Pubmed]
  7. An Arabidopsis cDNA encoding a bifunctional glutamine amidotransferase/cyclase suppresses the histidine auxotrophy of a Saccharomyces cerevisiae his7 mutant. Fujimori, K., Ohta, D. FEBS Lett. (1998) [Pubmed]
  8. Deletion analysis of domain independence in the TRP1 gene product of Neurospora crassa. Walker, M.S., DeMoss, J.A. Mol. Gen. Genet. (1990) [Pubmed]
  9. Expression and purification of imidazole glycerol phosphate synthase from Saccharomyces cerevisiae. Chittur, S.V., Chen, Y., Davisson, V.J. Protein Expr. Purif. (2000) [Pubmed]
  10. Regulation of the yeast HIS7 gene by the global transcription factor Abf1p. Springer, C., Krappmann, S., Künzler, M., Zmasek, C., Braus, G.H. Mol. Gen. Genet. (1997) [Pubmed]
 
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