2wm5

X-ray structure of the substrate-free Mycobacterium tuberculosis cytochrome P450 CYP124

spinqualitylabelsall models 2wm5, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2wm5 is a 1 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: HEM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CP124_MYCTU 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 Mycobacterium tuberculosis (Mtb) produces a variety of methyl-branched lipids that serve important functions, including modulating the immune response during pathogenesis and contributing to a robust cell wall that is impermeable to many chemical agents. Here, we report characterization of Mtb CYP124 (Rv2266) that includes demonstration of preferential oxidation of methyl-branched lipids. Spectrophotometric titrations and analysis of reaction products indicate that CYP124 tightly binds and hydroxylates these substrates at the chemically disfavored omega-position. We also report X-ray crystal structures of the ligand-free and phytanic acid-bound protein at a resolution of 1.5 A and 2.1 A, respectively, which provide structural insights into a cytochrome P450 with predominant omega-hydroxylase activity. The structures of ligand-free and substrate-bound CYP124 reveal several differences induced by substrate binding, including reorganization of the I helix and closure of the active site by elements of the F, G, and D helices that bind the substrate and exclude solvent from the hydrophobic active site cavity. The observed regiospecific catalytic activity suggests roles of CYP124 in the physiological oxidation of relevant Mtb methyl-branched lipids. The enzymatic specificity and structures reported here provide a scaffold for the design and testing of specific inhibitors of CYP124. Biochemical and structural characterization of CYP124: A methyl-branched lipid {omega}-hydroxylase from Mycobacterium tuberculosis.,Johnston JB, Kells PM, Podust LM, Ortiz de Montellano PR Proc Natl Acad Sci U S A. 2009 Nov 20. PMID:19933331 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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