4IHF

Chasing Acyl Carrier Protein Through a Catalytic Cycle of Lipid A Production

4IHF の概要

• エントリーDOI: 10.2210/pdb4ihf/pdb
• 関連するPDBエントリー: 4IHG 4IHH
• 分子名称: UDP-3-O-(3-hydroxymyristoyl)glucosamine N-acyltransferase, Acyl carrier protein, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: acyl carrier protein, left handed beta helix, lpxd, acyltransferase, lipid a, protein-protein complex, acp recognition domain, acp mediated product release, transferase-lipid binding protein complex, transferase/lipid binding protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 277988.48

構造登録者

Masoudi, A.,Raetz, C.R.H.,Pemble, C.W. (登録日: 2012-12-18, 公開日: 2013-11-13, 最終更新日: 2024-11-27)

主引用文献

Masoudi, A.,Raetz, C.R.,Zhou, P.,Pemble, C.W.
Chasing acyl carrier protein through a catalytic cycle of lipid A production.
Nature, 505:422-426, 2014

PubMed Abstract: Acyl carrier protein represents one of the most highly conserved proteins across all domains of life and is nature's way of transporting hydrocarbon chains in vivo. Notably, type II acyl carrier proteins serve as a crucial interaction hub in primary cellular metabolism by communicating transiently between partner enzymes of the numerous biosynthetic pathways. However, the highly transient nature of such interactions and the inherent conformational mobility of acyl carrier protein have stymied previous attempts to visualize structurally acyl carrier protein tied to an overall catalytic cycle. This is essential to understanding a fundamental aspect of cellular metabolism leading to compounds that are not only useful to the cell, but also of therapeutic value. For example, acyl carrier protein is central to the biosynthesis of the lipid A (endotoxin) component of lipopolysaccharides in Gram-negative microorganisms, which is required for their growth and survival, and is an activator of the mammalian host's immune system, thus emerging as an important therapeutic target. During lipid A synthesis (Raetz pathway), acyl carrier protein shuttles acyl intermediates linked to its prosthetic 4'-phosphopantetheine group among four acyltransferases, including LpxD. Here we report the crystal structures of three forms of Escherichia coli acyl carrier protein engaging LpxD, which represent stalled substrate and liberated products along the reaction coordinate. The structures show the intricate interactions at the interface that optimally position acyl carrier protein for acyl delivery and that directly involve the pantetheinyl group. Conformational differences among the stalled acyl carrier proteins provide the molecular basis for the association-dissociation process. An unanticipated conformational shift of 4'-phosphopantetheine groups within the LpxD catalytic chamber shows an unprecedented role of acyl carrier protein in product release.

PubMed: 24196711
DOI: 10.1038/nature12679

実験手法

X-RAY DIFFRACTION (2.1 Å)