3MJS

Structure of A-type Ketoreductases from Modular Polyketide Synthase

Summary for 3MJS

• Entry DOI: 10.2210/pdb3mjs/pdb
• Related: 3MJC 3MJE 3MJT 3MJV
• Descriptor: AmphB, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (2S)-2-hydroxybutanedioic acid, ... (6 entities in total)
• Functional Keywords: rossmann fold, oxidoreductase
• Biological source: Streptomyces nodosus
• Total number of polymer chains: 2
• Total formula weight: 105060.78

Authors

Zheng, J.,Taylor, C.A.,Piasecki, S.K.,Keatinge-Clay, A.T. (deposition date: 2010-04-13, release date: 2010-08-18, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.4 Å)