4l77

P450cin Active Site Water: Implications for Substrate Binding and Solvent Accessibility

spinqualitylabelsall models 4l77, resolution 1.38Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4l77 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. Method: X-ray diffraction, Resolution 1.379Å Ligands: CNL, HEM, PEG, PG4, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CINA_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. Publication Abstract from PubMed In P450cin, Tyr81, Asp241, Asn242, two water molecules, and the substrate participate in a complex H-bonded network. The role of this H-bonded network in substrate binding and catalysis has been probed by crystallography, spectroscopy, kinetics, isothermal titration calorimetry (ITC), and molecular dynamics. For the Y81F mutant, the substrate binds about 20-fold more weakly and Vmax decreases by about 30% in comparison to WT. The enhanced susceptibility of the heme to H2O2-mediated destruction in Y81F suggests that this mutant favors the open, low-spin conformational state. Asn242 H-bonds directly with the substrate, and replacing this residue with Ala results in water taking the place of the missing Asn side chain. This mutant exhibits a 70% decrease in activity. Crystal structures and molecular dynamics simulations of substrate-bound complexes show that the solvent has more ready access to the active site, especially for the N242A mutant. This accounts for about a 64% uncoupling of electron transfer from substrate hydroxylation. These data indicate the importance of the interconnected water network on substrate binding and on the open/closed conformational equilibrium, which are both critically important for maintaining high-coupling efficiency. P450cin Active Site Water: Implications for Substrate Binding and Solvent Accessibility.,Madrona Y, Hollingsworth SA, Khan B, Poulos TL Biochemistry. 2013 Jul 18. PMID:23829586 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cytochrome P450 3D structures

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