2-isopropylmalate synthase

In enzymology, a 2-isopropylmalate synthase () is an enzyme that catalyzes the chemical reaction
The three substrates of this enzyme are acetyl-CoA, 3-methyl-2-oxobutanoate, and H2O, and its products are (2S)-2-isopropylmalate and CoA.
The enzyme belongs to the family of transferases, specifically those acyltransferases that convert acyl groups into alkyl groups on transfer. The systematic name of this enzyme class is "acetyl-CoA:3-methyl-2-oxobutanoate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming)". Other names in common use include "3-carboxy-3-hydroxy-4-methylpentanoate 3-methyl-2-oxobutanoate-lyase", "(CoA-acetylating)", "alpha-isopropylmalate synthetase", "alpha-isopropylmalate synthase", "alpha-isopropylmalic synthetase", "isopropylmalate synthase", and "isopropylmalate synthetase". This enzyme participates in biosynthesis of -leucine and pyruvate metabolism. Monovalent and divalent cation activation have been reported for enzymes from different sources.
"Mycobacterium tuberculosis" α-isopropylmalate synthase requires a divalent metal ion, of which Mg2+ and Mn2+ give highest activity, and a monovalent cation, with K+ as the best activator. Zn2+ was shown to be an inhibitor, contrary to what was assumed from the structural data. In addition to the complex requirements for a divalent metal and further activation by K+, "M. tuberculosis" α-isopropylmalate synthase follows a random kinetic mechanism for catalysis. Another feature of the "M. tuberculosis" homolog is that -leucine, the feedback inhibitor, inhibits the enzyme in a time-dependent fashion. This was the first demonstration of a feedback inhibitor that displays slow-onset inhibition.
Structural studies.
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code .