3B70

Crystal structure of Aspergillus terreus trans-acting lovastatin polyketide enoyl reductase (LovC) with bound NADP

Summary for 3B70

• Entry DOI: 10.2210/pdb3b70/pdb
• Related: 3B6Z
• Descriptor: Enoyl reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: medium-chain reductase, rossmann fold, nadp-binding, ----, oxidoreductase
• Biological source: Aspergillus terreus
• Total number of polymer chains: 1
• Total formula weight: 41458.39

Authors

Ames, B.D.,Smith, P.T.,Ma, S.M.,Wong, E.W.,Xie, X.,Vederas, J.C.,Tang, Y.,Tsai, S.-C. (deposition date: 2007-10-29, release date: 2008-09-16, Last modification date: 2023-08-30)

Primary citation

Ames, B.D.,Nguyen, C.,Bruegger, J.,Smith, P.,Xu, W.,Ma, S.,Wong, E.,Wong, S.,Xie, X.,Li, J.W.,Vederas, J.C.,Tang, Y.,Tsai, S.C.
Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis.
Proc.Natl.Acad.Sci.USA, 109:11144-11149, 2012

PubMed Abstract: Lovastatin 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-Å 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.

PubMed: 22733743
DOI: 10.1073/pnas.1113029109

Experimental method

X-RAY DIFFRACTION (1.89 Å)