3hlf

Simvastatin Synthase (LovD), from Aspergillus terreus, S5 mutant, S76A mutant, complex with simvastatin

spinqualitylabelsall models 3hlf, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3hlf is a 1 chain structure with sequence from Aspte. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SIM Related: 3hle Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 PubMed Enzymes from natural product biosynthetic pathways are attractive candidates for creating tailored biocatalysts to produce semisynthetic pharmaceutical compounds. LovD is an acyltransferase that converts the inactive monacolin J acid (MJA) into the cholesterol-lowering lovastatin. LovD can also synthesize the blockbuster drug simvastatin using MJA and a synthetic alpha-dimethylbutyryl thioester, albeit with suboptimal properties as a biocatalyst. Here we used directed evolution to improve the properties of LovD toward semisynthesis of simvastatin. Mutants with improved catalytic efficiency, solubility, and thermal stability were obtained, with the best mutant displaying an approximately 11-fold increase in an Escherichia coli-based biocatalytic platform. To understand the structural basis of LovD enzymology, seven X-ray crystal structures were determined, including the parent LovD, an improved mutant G5, and G5 cocrystallized with ligands. Comparisons between the structures reveal that beneficial mutations stabilize the structure of G5 in a more compact conformation that is favorable for catalysis. Directed evolution and structural characterization of a simvastatin synthase.,Gao X, Xie X, Pashkov I, Sawaya MR, Laidman J, Zhang W, Cacho R, Yeates TO, Tang Y Chem Biol. 2009 Oct 30;16(10):1064-74. PMID:19875080 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Simvastatin Synthase

Proteopedia Page Contributors and Editors (what is this?)

OCA