2-isopropylmalate synthase

In enzymology, a 2-isopropylmalate synthase (EC number|2.3.3.13) is an enzyme that catalyzes the chemical reaction

:acetyl-CoA + 3-methyl-2-oxobutanoate + H₂O $ightleftharpoons$ (2S)-2-isopropylmalate + CoA

The 3 substrates of this enzyme are acetyl-CoA, 3-methyl-2-oxobutanoate, and H₂O, whereas its two products are (2S)-2-isopropylmalate and CoA.

This 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 leucine biosynthesis and pyruvate metabolism. Monovalent and divalent cation activation have been reported for enzymes from different sources.

"M. tuberculosis" α-isopropylmalate synthase was shown to require both a divalent metal, Mg²⁺ and Mn²⁺ give highest activity, and also 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 interesting feature of the "M. tuberculosis" homolog is that L-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.

tructural studies

As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code PDB link|1SR9.

References

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External links

::"The CAS registry number for this enzyme class is CAS registry|9030-98-2."

Gene Ontology (GO) codes