1ps9

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spinqualitylabelsall models 1ps9, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The Crystal Structure and Reaction Mechanism of E. coli 2,4-Dienoyl CoA Reductase

Overview

Escherichia coli 2,4-dienoyl-CoA reductase is an iron-sulfur flavoenzyme, required for the metabolism of unsaturated fatty acids with double bonds, at even carbon positions. The enzyme contains FMN, FAD, and a 4Fe-4S, cluster and exhibits sequence homology to another iron-sulfur, flavoprotein, trimethylamine dehydrogenase. It also requires NADPH as an, electron source, resulting in reduction of the C4-C5 double bond of the, acyl chain of the CoA thioester substrate. The structure presented here of, a ternary complex of E. coli 2,4-dienoyl-CoA reductase with NADP+ and a, fatty acyl-CoA substrate reveals a possible mechanism for substrate, reduction and provides details of a plausible electron transfer mechanism, involving both flavins and the iron-sulfur cluster. The reaction is, initiated by hydride transfer from NADPH to FAD, which in turn transfers, electrons, one at a time, to FMN via the 4Fe-4S cluster. In the final, stages of the reaction, the fully reduced FMN provides a hydride ion to, the C5 atom of substrate, and Tyr-166 and His-252 are proposed to form a, catalytic dyad that protonates the C4 atom of the substrate and complete, the reaction. Inspection of the substrate binding pocket explains the, relative promiscuity of the enzyme, catalyzing reduction of both, 2-trans,4-cis- and 2-trans,4-trans-dienoyl-CoA thioesters.

About this Structure

1PS9 is a Single protein structure of sequence from Escherichia coli with CL, SF4, FAD, FMN, NAP and MDE as ligands. Active as 2,4-dienoyl-CoA reductase (NADPH), with EC number 1.3.1.34 Full crystallographic information is available from OCA.

Reference

The crystal structure and reaction mechanism of Escherichia coli 2,4-dienoyl-CoA reductase., Hubbard PA, Liang X, Schulz H, Kim JJ, J Biol Chem. 2003 Sep 26;278(39):37553-60. Epub 2003 Jul 2. PMID:12840019

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