Kinetic analysis of the effects of monovalent cations and divalent metals on the activity of Mycobacterium tuberculosis α-isopropylmalate synthase

Luiz Pedro S. de Carvalho, John S. Blanchard

18 Scopus citations


Mycobacterium tuberculosis α-isopropylmalate synthase (MtIPMS) is a member of the family of enzymes that catalyze a Claisen-type condensation. In this work we characterized the monovalent and divalent specificity of MtIPMS using steady-state kinetics. The monovalent cation dependence of the kinetic parameters of substrates and divalent metals indicates that K+ is the likely physiological activator. K+ acts most likely as an allosteric activator, and exerts part of its effect through the catalytic divalent metal. The divalent metal specificity of MtIPMS is broad, and Mg2+ and Mn2+ are the metals that cause the highest activation. Interestingly, Zn2+, first assigned as the catalytic metal, inhibits the enzyme with submicromolar affinity. The features of monovalent cation and divalent metal activation, as well as the inhibition by Zn2+ and Cd2+, are discussed in light of the kinetic and structural information available for MtIPMS and other relevant enzymes.

Original languageEnglish (US)
Pages (from-to)141-148
Number of pages8
JournalArchives of Biochemistry and Biophysics
Issue number2
Publication statusPublished - Jul 15 2006



  • Activation
  • Divalent metal
  • Metal ion activation
  • Monovalent cation
  • Steady-state kinetics
  • Tuberculosis
  • l leucine
  • α-Isopropylmalate synthase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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