AI Article Synopsis
- - The study investigates how the Plm1 module of phoslactomycin polyketide synthase generates an activated cis-3-cyclohexylpropenoic acid through the ketoreduction of an L-3-hydroxyacyl-intermediate by an A-type ketoreductase (KR).
- - It is demonstrated that the KR domain, known as PlmKR1, successfully catalyzes the formation of the L-3-hydroxyacyl product, and its crystal structure shows a well-ordered active site with a distinctive Trp residue typical of A-type KRs.
- - A structural comparison reveals that PlmKR1's active site is ready for catalysis, unlike
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875705 | PMC |
| http://dx.doi.org/10.1016/j.chembiol.2013.04.014 | DOI Listing |
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