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Title: Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

Abstract

Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms 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.

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
914029
Report Number(s):
BNL-78597-2007-JA
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US0801486
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochem. Biophys. Res. Commun.; Journal Volume: 346; Journal Issue: 3
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; 43 PARTICLE ACCELERATORS; CARBOXYLIC ACIDS; CARNITINE; CHAINS; CRYSTAL STRUCTURE; CRYSTALLIZATION; DETERGENTS; ENZYMES; MEMBRANES; MITOCHONDRIA; RESOLUTION; SUBSTRATES; NSLS; national synchrotron light source

Citation Formats

Hsiao,Y., Jogl, G., Esser, V., and Tong, L. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II). United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.06.006.
Hsiao,Y., Jogl, G., Esser, V., & Tong, L. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II). United States. doi:10.1016/j.bbrc.2006.06.006.
Hsiao,Y., Jogl, G., Esser, V., and Tong, L. 2006. "Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)". United States. doi:10.1016/j.bbrc.2006.06.006.
@article{osti_914029,
title = {Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)},
author = {Hsiao,Y. and Jogl, G. and Esser, V. and Tong, L.},
abstractNote = {Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms 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.},
doi = {10.1016/j.bbrc.2006.06.006},
journal = {Biochem. Biophys. Res. Commun.},
number = 3,
volume = 346,
place = {United States},
year = 2006,
month = 1
}
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