3bdz

The Role of Asn 242 in P450cin

spinqualitylabelsall models 3bdz, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3bdz is a 2 chain structure with sequence from Citrobacter braakii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: HEM, MLI Related: 1t2b, 3be0 Gene: cinA (Citrobacter braakii) Resources: FirstGlance, OCA, RCSB, PDBsum Function [Q8VQF6_CITBR] Involved in the degradation of cineol (eucalyptol). Catalyzes the initial hydroxylation of cineole exclusively at the pro-R carbon to give the (S)-6beta-hydroxycineole. Cineole is the natural substrate of CinA. 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 Cytochrome P450cin (CYP176A1) is a bacterial P450 isolated from Citrobacter braakii that catalyzes the hydroxylation of cineole to (S)-6beta-hydroxycineole. This initiates the biodegradation of cineole, enabling C. braakii to live on cineole as its sole source of carbon and energy. P450cin lacks the almost universally conserved threonine residue believed to be involved in dioxygen activation and instead contains an asparagine at this position (Asn-242). To investigate the role of Asn-242 in P450cin catalysis, it was converted to alanine, and the resultant mutant was characterized. The characteristic CO-bound spectrum and spectrally determined K(D) for substrate binding were unchanged in the mutant. The x-ray crystal structures of the substrate-free and -bound N242A mutant were determined and show that the only significant change is in a reorientation of the substrate such that (R)-6alpha-hydroxycineole should be a major product. Molecular dynamics simulations of both wild type and mutant are consistent with the change in regio- and stereoselectivity predicted from the crystal structure. The mutation has only a modest effect on enzyme activity and on the diversion of the NADPH-reducing equivalent toward unproductive peroxide formation. Product profile analysis shows that (R)-6alpha-hydroxycineole is the main product, which is consistent with the crystal structure. These results demonstrate that Asn-242 is not a functional replacement for the conserved threonine in other P450s but, rather, is critical in controlling regioselective substrate oxidation. The critical role of substrate-protein hydrogen bonding in the control of regioselective hydroxylation in p450cin.,Meharenna YT, Slessor KE, Cavaignac SM, Poulos TL, De Voss JJ J Biol Chem. 2008 Apr 18;283(16):10804-12. Epub 2008 Feb 12. PMID:18270198 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450

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