Crystal structure of rat carnitine palmitoyltransferase II (CPT-II)

• Published in: Biochemical and biophysical research communications Vol. 346; no. 3; pp. 974 - 980
• Main Authors: Hsiao, Yu-Shan, Jogl, Gerwald, Esser, Victoria, Tong, Liang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.08.2006
• Subjects: Amino Acid Sequence; Animals; Binding Sites; CARBOXYLIC ACIDS; CARNITINE; Carnitine O-Palmitoyltransferase - chemistry; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - metabolism; CHAINS; CRYSTAL STRUCTURE; CRYSTALLIZATION; Crystallography, X-Ray; DETERGENTS; Diabetes; Disease; ENZYMES; Fatty acid metabolism; Hydrophobic and Hydrophilic Interactions; MATERIALS SCIENCE; MEMBRANES; MITOCHONDRIA; Mitochondria - chemistry; Mitochondria - metabolism; Models, Molecular; Molecular Sequence Data; Mutation - genetics; national synchrotron light source; NSLS; Obesity; PARTICLE ACCELERATORS; Protein structure; Protein Structure, Tertiary; Rats; RESOLUTION; Sequence Alignment; Structural Homology, Protein; SUBSTRATES; Obesity; Diabetes; Fatty acid metabolism; Protein structure
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.06.006

Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the β-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Å resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.