Crystal Structures of Murine Carnitine Acetyltransferase in Ternary Complexes with Its Substrates

Journal Article · Sun Jan 01 04:00:00 EST 2006 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M602622200· OSTI ID:929829

Hsiao, Y; Jogl, G; Tong, L

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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 929829
• Report Number(s): BNL--80387-2008-JA
• Journal Information: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Vol. 281; ISSN JBCHA3; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
CARBOXYLIC ACIDS
CARNITINE
COENZYMES
COMPLEXES
CRYSTAL STRUCTURE
DRUGS
ENERGY
ENZYMES
METABOLIC DISEASES
MITOCHONDRIA
MUTANTS
OXIDATION
SUBSTRATES
national synchrotron light source