4yof

DosS GAFA Domain Reduced Nitric Oxide Bound Crystal Structure

spinqualitylabelsall models 4yof, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yof is a 2 chain structure with sequence from Mycobacterium tuberculosis CDC1551. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.9Å Ligands: HEM, NO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DEVS_MYCTU Member of the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. May act as a redox sensor (rather than a direct hypoxia sensor); the normal (aerobic growth) state is the Fe(3+) form, while the reduced (anaerobic growth) Fe(2+) form is probably active for phosphate transfer. It is probably reduced by flavin nucleotides such as FMN and FAD. May be the primary sensor for CO. Donates a phosphate group to DevR (DosR). Publication Abstract from PubMed Defining the conformational states of cytochrome P450 active sites is critical for the design of agents that minimize drug-drug interactions, the development of isoform-specific P450 inhibitors, and the engineering of novel oxidative catalysts. We used two-dimensional (1)H,(15)N HSQC chemical shift perturbation mapping of (15)N-labeled Phe residues and x-ray crystallography to examine the ligand-dependent conformational dynamics of CYP119. Active site Phe residues were most affected by the binding of azole inhibitors and fatty acid substrates, in agreement with active site localization of the conformational changes. This was supported by crystallography, which revealed movement of the F-G loop with various azoles. Nevertheless, the NMR chemical shift perturbations caused by azoles and substrates were distinguishable. The absence of significant chemical shift perturbations with several azoles revealed binding of ligands to an open conformation similar to that of the ligand-free state. In contrast, 4-phenylimidazole caused pronounced NMR changes involving Phe-87, Phe-144, and Phe-153 that support the closed conformation found in the crystal structure. The same closed conformation is observed by NMR and crystallography with a para-fluoro substituent on the 4-phenylimidazole, but a para-chloro or bromo substituent engendered a second closed conformation. An open conformation is thus favored in solution with many azole ligands, but para-substituted phenylimidazoles give rise to two closed conformations that depend on the size of the para-substituent. The results suggest that ligands selectively stabilize discrete cytochrome P450 conformational states. Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography.,Basudhar D, Madrona Y, Kandel S, Lampe JN, Nishida CR, de Montellano PR J Biol Chem. 2015 Apr 17;290(16):10000-17. doi: 10.1074/jbc.M114.627935. Epub, 2015 Feb 10. PMID:25670859 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Response regulator 3D structure

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