3b70
From Proteopedia
Crystal structure of Aspergillus terreus trans-acting lovastatin polyketide enoyl reductase (LovC) with bound NADP
Structural highlights
Function[LOVC_ASPTE] Catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the LovB-mediated biosynthesis of the lovastatin nonaketide chain.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedLovastatin is an important statin prescribed for the treatment and prevention of cardiovascular diseases. Biosynthesis of lovastatin uses an iterative type I polyketide synthase (PKS). LovC is a trans-acting enoyl reductase (ER) that specifically reduces three out of eight possible polyketide intermediates during lovastatin biosynthesis. Such trans-acting ERs have been reported across a variety of other fungal PKS enzymes as a strategy in nature to diversify polyketides. How LovC achieves such specificity is unknown. The 1.9-A structure of LovC reveals that LovC possesses a medium-chain dehydrogenase/reductase (MDR) fold with a unique monomeric assembly. Two LovC cocrystal structures and enzymological studies help elucidate the molecular basis of LovC specificity, define stereochemistry, and identify active-site residues. Sequence alignment indicates a general applicability to trans-acting ERs of fungal PKSs, as well as their potential application to directing biosynthesis. Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis.,Ames BD, Nguyen C, Bruegger J, Smith P, Xu W, Ma S, Wong E, Wong S, Xie X, Li JW, Vederas JC, Tang Y, Tsai SC Proc Natl Acad Sci U S A. 2012 Jun 25. PMID:22733743[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Aspte | Large Structures | Ames, B D | Ma, S M | Smith, P T | Tang, Y | Tsai, S C | Vederas, J C | Wong, E W | Xie, X | Medium-chain reductase | Nadp-binding | Oxidoreductase | Rossmann fold
