Biology:2-isopropylmalate synthase
| 2-isopropylmalate synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 2.3.3.13 | ||||||||
| CAS number | 9030-98-2 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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In enzymology, a 2-isopropylmalate synthase (EC 2.3.3.13) is an enzyme that catalyzes the chemical reaction
- acetyl-CoA + 3-methyl-2-oxobutanoate + H2O [math]\displaystyle{ \rightleftharpoons }[/math] (2S)-2-isopropylmalate + CoA
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 L-leucine and pyruvate metabolism. Monovalent and divalent cation activation have been reported for enzymes from different sources.[1][2][3]
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.[4][5] 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.[6]
Structural studies
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code 1SR9.
References
- ↑ "Absolute configuration of alpha isopropylmalate and the mechanism of its conversion to beta isopropylmalate in the biosynthesis of leucine". Biochemistry 12 (17): 3346–50. 1973. doi:10.1021/bi00741a031. PMID 4270046.
- ↑ "Alpha-isopropylmalate synthase from Salmonella typhimurium Purification and properties". J. Biol. Chem. 244 (8): 2218–25. 1969. PMID 4976555.
- ↑ 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 (11): 2309–2327. doi:10.1021/bi00887a008.
- ↑ "Kinetic and Chemical Mechanism of alpha-Isopropylmalate Synthase from Mycobacterium tuberculosis". Biochemistry 45 (29): 8988–99. 2006. doi:10.1021/bi0606602. PMID 16846242.
- ↑ "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 (2): 141–48. 2006. doi:10.1016/j.abb.2006.03.030. PMID 16684501.
- ↑ "Slow-onset Feedback Inhibition: Inhibition of Mycobacterium tuberculosis alpha-Isopropylmalate Synthase by L-Leucine". Journal of the American Chemical Society 127 (28): 10004–5. 2005. doi:10.1021/ja052513h. PMID 16011356.
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