The 1.3 Å crystal structure of human mitochondrial Δ3-Δ2-enoyl-CoA isomerase shows a novel mode of binding for the fatty acyl group

被引:37
作者
Partanen, ST
Novikov, DK
Popov, AN
Mursula, AM
Hiltunen, JK
Wierenga, RK
机构
[1] Univ Oulu, Bioctr Oulu, FIN-90014 Oulu, Finland
[2] Univ Oulu, Dept Biochem, FIN-90014 Oulu, Finland
[3] DESY, European Mol Biol Lab, D-2000 Hamburg, Germany
[4] Russian Acad Sci, AV Shubnikov Crystallog Inst, Moscow 117333, Russia
基金
芬兰科学院;
关键词
Delta(3)Delta(2)-enoyl-CoA isomerase; crotonase fold; octanoyl-CoA; beta-oxidation; mitochondria;
D O I
10.1016/j.jmb.2004.07.039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The crystal structure of Delta(3)-Delta(2)-enoyl-CoA isomerase from human mitochondria (hmEci), complexed with the substrate analogue octanoyl-CoA, has been refined at 1.3Angstrom resolution. This enzyme takes part in the beta-oxidation of unsaturated fatty acids by converting both cis-3 and trans-3-enoyl-CoA esters (with variable length of the acyl group) to trans-2-enoyl-CoA. hmEci belongs to the hydratase/isomerase (crotonase) superfamily. Most of the enzymes belonging to this superfamily are hexamers, but hmEci is shown to be a trimer. The mode of binding of the ligand, octanoyl-CoA, shows that the omega-end of the acyl group binds in a hydrophobic tunnel formed by residues of the loop preceding helix H4 as well as by side-chains of the kinked helix H9. From the structure of the complex it can be seen that Glu136 is the only catalytic residue. The importance of Glu136 for catalysis is confirmed by mutagenesis studies. A cavity analysis shows the presence of two large, adjacent empty hydrophobic cavities near the active site, which are shaped by side-chains of helices H1, H2, H3 and H4. The structure comparison of hmEci with structures of other superfamily members, in particular of rat mitochondrial hydratase (crotonase) and yeast peroxisomal enoyl-CoA isomerase, highlights the variable mode of binding of the fatty acid moiety in this superfamily. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1197 / 1208
页数:12
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