5XWV

Substrate-bound Structure of a Ketoreductase from the Second Module of the amphotericin Polyketide Synthases

5XWV の概要

• エントリーDOI: 10.2210/pdb5xwv/pdb
• 分子名称: AmphB, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, S-[2-[3-[[(2R)-3,3-dimethyl-2,4-bis(oxidanyl)butanoyl]amino]propanoylamino]ethyl] (2R)-2-methyl-3-oxidanylidene-pentanethioate, ... (4 entities in total)
• 機能のキーワード: modular polyketide synthease, ketoreductase, oxidoreductase
• 由来する生物種: Streptomyces nodosus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 105121.23

構造登録者

Liu, C.,Zheng, J. (登録日: 2017-06-30, 公開日: 2018-06-06, 最終更新日: 2023-11-22)

主引用文献

Liu, C.,Yuan, M.,Xu, X.,Wang, L.,Keatinge-Clay, A.T.,Deng, Z.,Lin, S.,Zheng, J.
Substrate-bound structures of a ketoreductase from amphotericin modular polyketide synthase.
J. Struct. Biol., 203:135-141, 2018

PubMed Abstract: Ketoreductase (KR) domains of modular polyketide synthases (PKSs) control the stereochemistry of C2 methyl and C3 hydroxyl substituents of polyketide intermediates. To understand the molecular basis of stereocontrol exerted by KRs, the crystal structure of a KR from the second module of the amphotericin PKS (AmpKR2) complexed with NADP and 2-methyl-3-oxopentanoyl-pantetheine was solved. This first ternary structure provides direct evidence to the hypothesis that a substrate enters into the active site of an A-type KR from the side opposite the coenzyme to generate an L-hydroxyl substituent. A comparison with the ternary complex of a G355T/Q364H mutant sheds light on the structural basis for stereospecificity toward the substrate C2 methyl substituent. Functional assays suggest the pantetheine handle shows obvious influence on the catalytic efficiency and the stereochemical outcome. Together, these findings extend our current understanding of the stereochemical control of PKS KR domains.

PubMed: 29626512
DOI: 10.1016/j.jsb.2018.04.001

実験手法

X-RAY DIFFRACTION (1.8 Å)