Nucleotide-dependent tetramerizat1on of yeast CTP synthetase

A. Pappas, W. L. Yang, T. S. Park, G. M. Carman

Research output: Contribution to journalArticle

Abstract

The nucleotide-dependent tetramerization of purified native CTP synthetasc from yeast was characterized. CTP synthetase existed as a dimer in the ab scnce of ATP and UTP. In the presence of saturating concentrations of AT P and UTP, CTP synthetase existed as a t et ramer. Increasing concern rations of ATP and UTP caused a dose-dependent conversion of the dirnerir species to a tetramer. F.nzyrne tetramerization correlated with the kinetics of enzyme activity. The tetramerization of CTP synthetase was dependent on UTP and magnesium ions. ATP facilitated the UTP-dependent tetramerization of CTP synthetase by a mechanism that involved the ATP-dependent phosphorylation of UTP catalyzed by the enzyme. The glutaminase reaction that is catalyzed by the enzyme was not required for enzyme tetramerization. Phosphorylation of the purified native CTP synthetase with protein kinase A and with protein kinase C facilitated the nucleotide-dependent tetramerization. Dephos phorylation of native CTP synthetase with alkaline phosphatase prevented the nucleotide-dependem tetramerization of the enzyme. This correlated with the inactivation of CTP synthetase activity after dephosphorylation. Rephosphory lation of the dephosphorylated enzyme with protein kinase A and with protein kinase C resulted in a partial restoration of both CTP synthetase activity and nucleotide-dependent tetramerization, Taken together, these results indicated that enzyme tetramerization was required for CTP synthetase activity and that enzyme phosphorylation played an important role in the tetramerization and regulation of the enzyme. Supported by NIH grant CM-50679.

Original languageEnglish (US)
Pages (from-to)A1285
JournalFASEB Journal
Volume12
Issue number8
StatePublished - Dec 1 1998

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Pappas, A., Yang, W. L., Park, T. S., & Carman, G. M. (1998). Nucleotide-dependent tetramerizat1on of yeast CTP synthetase. FASEB Journal, 12(8), A1285.