4HXY

PlmKR1-Ketoreductase from the first module of phoslactomycin biosynthesis in Streptomyces sp. HK803

Summary for 4HXY

• Entry DOI: 10.2210/pdb4hxy/pdb
• Descriptor: Plm1, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 6-AMINOHEXANOIC ACID, ... (4 entities in total)
• Functional Keywords: short chain dehydrogenase/reductase, ketoreductase, rossmann fold, oxidoreductase
• Biological source: Streptomyces sp. HK803
• Total number of polymer chains: 2
• Total formula weight: 92701.95

Authors

Whicher, J.R.,Smith, J.L. (deposition date: 2012-11-12, release date: 2013-07-10, Last modification date: 2023-11-15)

Primary citation

Bonnett, S.A.,Whicher, J.R.,Papireddy, K.,Florova, G.,Smith, J.L.,Reynolds, K.A.
Structural and Stereochemical Analysis of a Modular Polyketide Synthase Ketoreductase Domain Required for the Generation of a cis-Alkene.
Chem.Biol., 20:772-783, 2013

PubMed Abstract: The formation of an activated cis-3-cyclohexylpropenoic acid by Plm1, the first extension module of the phoslactomycin polyketide synthase, is proposed to occur through an L-3-hydroxyacyl-intermediate as a result of ketoreduction by an A-type ketoreductase (KR). Here, we demonstrate that the KR domain of Plm1 (PlmKR1) catalyzes the formation of an L-3-hydroxyacyl product. The crystal structure of PlmKR1 revealed a well-ordered active site with a nearby Trp residue characteristic of A-type KRs. Structural comparison of PlmKR1 with B-type KRs that produce D-3-hydroxyacyl intermediates revealed significant differences. The active site of cofactor-bound A-type KRs is in a catalysis-ready state, whereas cofactor-bound B-type KRs are in a precatalytic state. Furthermore, the closed lid loop in substrate-bound A-type KRs restricts active site access from all but one direction, which is proposed to control the stereochemistry of ketoreduction.

PubMed: 23790488
DOI: 10.1016/j.chembiol.2013.04.014

Experimental method

X-RAY DIFFRACTION (1.68 Å)