Abstract
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 language | English (US) |
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Pages (from-to) | 141-148 |
Number of pages | 8 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 451 |
Issue number | 2 |
DOIs | |
State | Published - Jul 15 2006 |
Keywords
- 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