2h3p
Crystal structure of murine carnitine acetyltransferase in complex with carnitine and acetyl-CoA
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OverviewOverview
Carnitine acyltransferases catalyze the reversible exchange of acyl groups between coenzyme A (CoA) and carnitine. They have important roles in many cellular processes, especially the oxidation of long-chain fatty acids in the mitochondria for energy production, and are attractive targets for drug discovery against diabetes and obesity. To help define in molecular detail the catalytic mechanism of these enzymes, we report here the high resolution crystal structure of wild-type murine carnitine acetyltransferase (CrAT) in a ternary complex with its substrates acetyl-CoA and carnitine, and the structure of the S554A/M564G double mutant in a ternary complex with the substrates CoA and hexanoylcarnitine. Detailed analyses suggest that these structures may be good mimics for the Michaelis complexes for the forward and reverse reactions of the enzyme, representing the first time that such complexes of CrAT have been studied in molecular detail. The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general.
About this StructureAbout this Structure
2H3P is a Single protein structure of sequence from Mus musculus with , and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of murine carnitine acetyltransferase in ternary complexes with its substrates., Hsiao YS, Jogl G, Tong L, J Biol Chem. 2006 Sep 22;281(38):28480-7. Epub 2006 Jul 26. PMID:16870616
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