Influence of allosteric regulators on individual steps in the reaction catalyzed by mycobacterium tuberculosis 2-hydroxy-3-oxoadipate synthase

Anand Balakrishnan, Frank Jordan, Carl F. Nathan

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: 2-Hydroxy-3-oxoadipate synthase is predicted to be essential for growth of Mycobacterium tuberculosis and is subject to allosteric regulation. Results: The role of regulators was characterized by kinetics and detection of thiamin diphosphate-bound covalent intermediate distribution. Conclusion: AcCoA activates steps leading to a predecarboxylation intermediate; GarA chiefly inhibits postdecarboxylation steps. Significance: This novel regulatory regime in thiamin diphosphate enzymes provides new leads to inhibition.

Original languageEnglish (US)
Pages (from-to)21688-21702
Number of pages15
JournalJournal of Biological Chemistry
Volume288
Issue number30
DOIs
StatePublished - Jul 26 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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