2whw | pdb_00002whw

Selective oxidation of carbolide C-H bonds by engineered macrolide P450 monooxygenase

spinqualitylabelsall models 2whw, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2whw is a 2 chain structure with sequence from As 4.1526. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1D4, HEM, SO4 Related: 2cd8, 2wi9, 2ca0, 2bvj, 2vzm, 2c7x, 2vz7, 2c6h 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 Regio- and stereoselective oxidation of an unactivated C-H bond remains a central challenge in organic chemistry. Considerable effort has been devoted to identifying transition metal complexes, biological catalysts, or simplified mimics, but limited success has been achieved. Cytochrome P450 mono-oxygenases are involved in diverse types of regio- and stereoselective oxidations, and represent a promising biocatalyst to address this challenge. The application of this class of enzymes is particularly significant if their substrate spectra can be broadened, selectivity controlled, and reactions catalyzed in the absence of expensive heterologous redox partners. In this study, we engineered a macrolide biosynthetic P450 mono-oxygenase PikC (PikC(D50N)-RhFRED) with remarkable substrate flexibility, significantly increased activity compared to wild-type enzyme, and self-sufficiency. By harnessing its unique desosamine-anchoring functionality via a heretofore under-explored "substrate engineering" strategy, we demonstrated the ability of PikC to hydroxylate a series of carbocyclic rings linked to the desosamine glycoside via an acetal linkage (referred to as "carbolides") in a regioselective manner. Complementary analysis of a number of high-resolution enzyme-substrate cocrystal structures provided significant insights into the function of the aminosugar-derived anchoring group for control of reaction site selectivity. Moreover, unexpected biological activity of a select number of these carbolide systems revealed their potential as a previously unrecorded class of antibiotics. Selective oxidation of carbolide C-H bonds by an engineered macrolide P450 mono-oxygenase.,Li S, Chaulagain MR, Knauff AR, Podust LM, Montgomery J, Sherman DH Proc Natl Acad Sci U S A. 2009 Oct 15. PMID:19833867 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA