4DBZ

Crystal Structure of V151L Actinorhodin Polyketide Ketoreductase with NADPH

4DBZ の概要

• エントリーDOI: 10.2210/pdb4dbz/pdb
• 関連するPDBエントリー: 4DC0 4DC1
• 分子名称: Ketoacyl reductase, 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 coelicolor
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60447.62

構造登録者

Javidpour, P.,Tsai, S.-C. (登録日: 2012-01-16, 公開日: 2013-01-16, 最終更新日: 2024-02-28)

主引用文献

Javidpour, P.,Bruegger, J.,Srithahan, S.,Korman, T.P.,Crump, M.P.,Crosby, J.,Burkart, M.D.,Tsai, S.C.
The Determinants of Activity and Specificity in Actinorhodin Type II Polyketide Ketoreductase.
Chem.Biol., 20:1225-1234, 2013

PubMed Abstract: In the actinorhodin type II polyketide synthase, the first polyketide modification is a regiospecific C9-carbonyl reduction, catalyzed by the ketoreductase (actKR). Our previous studies identified the actKR 94-PGG-96 motif as a determinant of stereospecificity. The molecular basis for reduction regiospecificity is, however, not well understood. In this study, we examined the activities of 20 actKR mutants through a combination of kinetic studies, PKS reconstitution, and structural analyses. Residues have been identified that are necessary for substrate interaction, and these observations have suggested a structural model for this reaction. Polyketides dock at the KR surface and are steered into the enzyme pocket where C7-C12 cyclization is mediated by the KR before C9-ketoreduction can occur. These molecular features can potentially serve as engineering targets for the biosynthesis of novel, reduced polyketides.

PubMed: 24035284
DOI: 10.1016/j.chembiol.2013.07.016

実験手法

X-RAY DIFFRACTION (2.643 Å)