6OKC

Crosslinked Crystal Structure of Type II Fatty Acid Synthase Ketosynthase, FabB, and C12-crypto Acyl Carrier Protein, AcpP

6OKC の概要

• エントリーDOI: 10.2210/pdb6okc/pdb
• 分子名称: 3-oxoacyl-[acyl-carrier-protein] synthase 1, Acyl carrier protein, N-[2-(dodecanoylamino)ethyl]-N~3~-[(2R)-2-hydroxy-3,3-dimethyl-4-(phosphonooxy)butanoyl]-beta-alaninamide, ... (4 entities in total)
• 機能のキーワード: thiolase, ketosynthase, ks, acpp, transferase-lipid transport complex, transferase/lipid transport
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 103650.53

構造登録者

Mindrebo, J.T.,Kim, W.E.,Bartholow, T.G.,Chen, A.,Davis, T.D.,La Clair, J.,Burkart, M.D.,Noel, J.P. (登録日: 2019-04-12, 公開日: 2020-04-15, 最終更新日: 2024-11-06)

主引用文献

Mindrebo, J.T.,Patel, A.,Kim, W.E.,Davis, T.D.,Chen, A.,Bartholow, T.G.,La Clair, J.J.,McCammon, J.A.,Noel, J.P.,Burkart, M.D.
Gating mechanism of elongating beta-ketoacyl-ACP synthases.
Nat Commun, 11:1727-1727, 2020

PubMed Abstract: Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs and choreograph a ping-pong mechanism, often in an iterative fashion. Here, we report crystal structures of substrate mimetic bearing ACPs in complex with the elongating KSs from Escherichia coli, FabF and FabB, in order to better understand the stereochemical features governing substrate discrimination by KSs. Complemented by molecular dynamics (MD) simulations and mutagenesis studies, these structures reveal conformational states accessed during KS catalysis. These data taken together support a gating mechanism that regulates acyl-ACP binding and substrate delivery to the KS active site. Two active site loops undergo large conformational excursions during this dynamic gating mechanism and are likely evolutionarily conserved features in elongating KSs.

PubMed: 32265440
DOI: 10.1038/s41467-020-15455-x

実験手法

X-RAY DIFFRACTION (1.55 Å)