1t7o

Crystal structure of the M564G mutant of murine carnitine acetyltransferase in complex with carnitine

spinqualitylabelsall models 1t7o, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1t7o is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 152 Related: 1ndb, 1ndf, 1ndi, 1t7n, 1t7q Activity: Carnitine O-acetyltransferase, with EC number 2.3.1.7 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CACP_MOUSE] Carnitine acetylase is specific for short chain fatty acids. Carnitine acetylase seems to affect the flux through the pyruvate dehydrogenase complex. It may be involved as well in the transport of acetyl-CoA into mitochondria. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Carnitine acyltransferases catalyze the 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, and are attractive targets for drug discovery against diabetes and obesity. These enzymes are classified based on their substrate selectivity for short-chain, medium-chain, or long-chain fatty acids. Structural information on carnitine acetyltransferase suggests that residues Met-564 and Phe-565 may be important determinants of substrate selectivity with the side chain of Met-564 located in the putative binding pocket for acyl groups. Both residues are replaced by glycine in carnitine palmitoyltransferases. To assess the functional relevance of this structural observation, we have replaced these two residues with small amino acids by mutagenesis, characterized the substrate preference of the mutants, and determined the crystal structures of two of these mutants. Kinetic studies confirm that the M564G or M564A mutation is sufficient to increase the activity of the enzyme toward medium-chain substrates with hexanoyl-CoA being the preferred substrate for the M564G mutant. The crystal structures of the M564G mutant, both alone and in complex with carnitine, reveal a deep binding pocket that can accommodate the larger acyl group. We have determined the crystal structure of the F565A mutant in a ternary complex with both the carnitine and CoA substrates at a 1.8-A resolution. The F565A mutation has minor effects on the structure or the substrate preference of the enzyme. Structural and biochemical studies of the substrate selectivity of carnitine acetyltransferase.,Hsiao YS, Jogl G, Tong L J Biol Chem. 2004 Jul 23;279(30):31584-9. Epub 2004 May 21. PMID:15155726 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carnitine acetyltransferase

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