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Molecular dynamics simulations of beta-ketoacyl-, beta-hydroxyacyl-, and trans-2-enoyl-acyl carrier proteins of Escherichia coli.

Abstract：

:Acyl carrier protein (ACP) is the central player in fatty acid (FA) biosynthesis. It covalently binds all FA intermediates and presents them to the enzymes needed for elongation. Bacterial ACP must interact with a large number of proteins, which raises the question of how different acyl-ACPs are recognized and distinguished from each other. We performed molecular dynamics (MD) simulations of the FA synthase intermediates beta-ketoacyl-, beta-hydroxyacyl, and trans-2-enoyl-ACP spanning from 4 to 18 carbon groups in length. These forms of acyl-ACP have largely yet to be characterized experimentally, and our simulations provide a first insight into these structures. The simulations were conducted with the acyl chain directed into the solvent, as well as in a solvent-protected conformation inside the hydrophobic pocket of Escherichia coli ACP. Spontaneous migration from the solvent-exposed state into the hydrophobic binding pocket of ACP was seen in each of the intermediate classes studied, but not in all the individual simulations. This confirms that the intermediates can enter and utilize the same hydrophobic pockets as saturated acyl chains. In addition, a recurring, novel association of the acyl chains with loop I of ACP was observed that may be occupied transiently before entry into the hydrophobic pocket. The MD simulations of the acyl chains in a solvent-shielded state reveal that the polar functional group in the beta position of the beta-ketoacyl and beta-hydroxyacyl chains anchors these moieties at the cavity entrance, while the chains without a polar group in the beta position lack this additional anchoring atom. This leads to a binding mode in which the beta-ketoacyl and beta-hydroxyacyl chains are positioned further from the bottom of the pocket compared to the saturated and enoyl chains, particularly in short chain (

journal_name

Biochemistry

journal_title

Biochemistry

authors

Chan DI,Tieleman DP,Vogel HJ

doi

10.1021/bi901713r

subject

Has Abstract

pub_date

2010-04-06 00:00:00

pages

2860-8

issue

eissn

0006-2960

issn

1520-4995

journal_volume

pub_type

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Molecular dynamics simulations of beta-ketoacyl-, beta-hydroxyacyl-, and trans-2-enoyl-acyl carrier proteins of Escherichia coli.