2-isopropylmalate synthase

InterPro Family 2-isopropylmalate synthase 2.3.3.13 9030-98-2 0003852 2-isopropylmalate synthase (2.3.3.13) is an enzyme that catalyzes the chemical reaction 75% α-Ketoisovaleric acid class=skin-invert-image Acetyl-CoA H2O Q76280927 (S)-2-isopropylmalic acid + Coenzyme A The three substrates of this enzyme are α-ketoisovaleric acid, acetyl-CoA, and water. Its products are the (S) enantiomer of 2-isopropylmalic acid and coenzyme A.Cole FE, Kalyanpur MG, Stevens CM 1973 Absolute configuration of alpha isopropylmalate and the mechanism of its conversion to beta isopropylmalate in the biosynthesis of leucine Biochemistry 12 3346–50 4270046 10.1021/bi00741a031 17 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 L-leucine and pyruvate metabolism. Monovalent and divalent cation activation have been reported for enzymes from different sources.Kohlhaw G, Leary TR, Umbarger HE 1969 Alpha-isopropylmalate synthase from Salmonella typhimurium Purification and properties J. Biol. Chem. 244 2218–25 4976555 8 10.1016/S0021-9258(18)97789-6 free Webster RE Gross, SR 1965 The alpha-isopropylmalate synthetase of Neurospora. I. The kinetics and end product control of alpha-isopropylmalate synthetase function Biochemistry 4 2309–2327 10.1021/bi00887a008 11 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.Carvalho LP, Blanchard, JS 2006 Kinetic and Chemical Mechanism of alpha-Isopropylmalate Synthase from Mycobacterium tuberculosis Biochemistry 45 8988–99 16846242 10.1021/bi0606602 29 2507874 Carvalho LP, Blanchard, JS 2006 Kinetic analysis of the effects of monovalent cations and divalent metals on the activity of Mycobacterium tuberculosis alpha-isopropylmalate synthase Archives of Biochemistry and Biophysics 451 141–48 16684501 10.1016/j.abb.2006.03.030 2 Zn2+ was shown to be an inhibitor, contrary to what was assumed from the structural data. Another 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.Carvalho LP, Argyrou A, Blanchard, JS 2005 Slow-onset Feedback Inhibition: Inhibition of Mycobacterium tuberculosis alpha-Isopropylmalate Synthase by L-Leucine Journal of the American Chemical Society 127 10004–5 16011356 10.1021/ja052513h 28 2005JAChS.12710004D Tertiary structure As of late 2007, only one tertiary structure has been solved for this class of enzymes, with the Protein Data Bank accession code 1SR9. References 1 Biology no Category:EC 2.3.3 Category:Potassium enzymes Category:Enzymes of known structure