4L4X

An A2-type ketoreductase from a modular polyketide synthase

「4DI7」から置き換えられました

4L4X の概要

• エントリーDOI: 10.2210/pdb4l4x/pdb
• 関連するPDBエントリー: 2FR0 2Z5L 3MJS
• 分子名称: AmphI, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (3 entities in total)
• 機能のキーワード: rossmann fold, ketoreductase, oxidoreductase
• 由来する生物種: Streptomyces nodosus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 62072.74

構造登録者

Zheng, J.,Keatinge-Clay, A.T. (登録日: 2013-06-10, 公開日: 2013-06-19, 最終更新日: 2023-09-20)

主引用文献

Zheng, J.,Piasecki, S.K.,Keatinge-Clay, A.T.
Structural Studies of an A2-Type Modular Polyketide Synthase Ketoreductase Reveal Features Controlling alpha-Substituent Stereochemistry.
Acs Chem.Biol., 8:1964-1971, 2013

PubMed Abstract: Modular polyketide synthase ketoreductases often set two stereocenters when reducing intermediates in the biosynthesis of a complex polyketide. Here we report the 2.55-Å resolution structure of an A2-type ketoreductase from the 11th module of the amphotericin polyketide synthase that sets a combination of l-α-methyl and l-β-hydroxyl stereochemistries and represents the final catalytically competent ketoreductase type to be structurally elucidated. Through structure-guided mutagenesis a double mutant of an A1-type ketoreductase was generated that functions as an A2-type ketoreductase on a diketide substrate analogue, setting an α-alkyl substituent in an l-orientation rather than in the d-orientation set by the unmutated ketoreductase. When the activity of the double mutant was examined in the context of an engineered triketide lactone synthase, the anticipated triketide lactone was not produced even though the ketoreductase-containing module still reduced the diketide substrate analogue as expected. These findings suggest that re-engineered ketoreductases may be catalytically outcompeted within engineered polyketide synthase assembly lines.

PubMed: 23755878
DOI: 10.1021/cb400161g

実験手法

X-RAY DIFFRACTION (2.55 Å)