3MJS

Structure of A-type Ketoreductases from Modular Polyketide Synthase

3MJS の概要

• エントリーDOI: 10.2210/pdb3mjs/pdb
• 関連するPDBエントリー: 3MJC 3MJE 3MJT 3MJV
• 分子名称: AmphB, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (2S)-2-hydroxybutanedioic acid, ... (6 entities in total)
• 機能のキーワード: rossmann fold, 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: 105060.78

構造登録者

Zheng, J.,Taylor, C.A.,Piasecki, S.K.,Keatinge-Clay, A.T. (登録日: 2010-04-13, 公開日: 2010-08-18, 最終更新日: 2023-09-06)

主引用文献

Zheng, J.,Taylor, C.A.,Piasecki, S.K.,Keatinge-Clay, A.T.
Structural and Functional Analysis of A-Type Ketoreductases from the Amphotericin Modular Polyketide Synthase.
Structure, 18:913-922, 2010

PubMed Abstract: Complex polyketides are characterized by multiple chiral centers harboring hydroxyl and alkyl substituents. To investigate the mechanisms by which these stereocenters are set, several high-resolution structures of the ketoreductase (KR) domain from the second module of the amphotericin modular polyketide synthase (PKS) were solved. This first structural analysis of an A-type KR helps reveal how these KRs direct polyketide intermediates into their active sites from the side opposite that used by B-type KRs, resulting in a beta-hydroxyl group of opposite stereochemistry. A comparison of structures obtained in the absence and presence of ligands reveals an induced fit mechanism that is important for catalysis. Activity assays of mutants of KRs from the first and second modules of the amphotericin PKS reveal the relative contributions of several active site residues toward catalysis and stereocontrol. Together, these results highlight the possibility of region-specific modification of polyketides through active site engineering of KRs.

PubMed: 20696392
DOI: 10.1016/j.str.2010.04.015

実験手法

X-RAY DIFFRACTION (1.4 Å)