2d0e
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(New page: 200px<br /><applet load="2d0e" size="350" color="white" frame="true" align="right" spinBox="true" caption="2d0e, resolution 2.150Å" /> '''Substrate assited i...)
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Revision as of 16:52, 29 January 2008
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Substrate assited in Oxygen Activation in Cytochrome P450 158A2
Overview
From the x-ray crystal structure of CYP158A2 (Zhao, B., Guengerich, F. P., Bellamine, A., Lamb, D. C., Izumikawa, M., Lei, L., Podust, L. M., Sundaramoorthy, M., Reddy, L. M., Kelly, S. L., Kalaitzis, J. A., Stec, D., Voehler, M., Falck, J. R., Moore, B. S., Shimada, T., and Waterman, M., R. (2005) J. Biol. Chem. 280, 11599-11607), one of 18 cytochrome P450, (CYP) genes in the actinomycete Streptomyces coelicolor, ordered active, site water molecules (WAT505, WAT600, and WAT640), and hydroxyl groups of, the substrate flaviolin were proposed to participate in proton transfer, and oxygen cleavage in this monooxygenase. To probe their roles in, catalysis, we have studied the crystal structures of a substrate analogue, (2-hydroxy-1,4-naphthoquinone) complex with ferric CYP158A2 (2.15 A) and, the flaviolin ferrous dioxygen-bound CYP158A2 complex (1.8 A). Catalytic, activity toward 2-hydroxy-1,4-naphthoquinone was approximately 70-fold, less than with flaviolin. In the ferrous dioxygen-bound flaviolin complex, the three water molecules in the ferric flaviolin complex still occupy the, same positions and form hydrogen bonds to the distal dioxygen atom. These, findings suggest that CYP158A2 utilizes substrate hydroxyl groups to, stabilize active site water and further assist in the iron-linked dioxygen, activation. A continuous hydrogen-bonded water network connecting the, active site to the protein surface (bulk solvent) not present in the other, two ferrous dioxygen-bound P450 structures (CYP101A1/P450cam and, CYP107A1/P450eryF) is proposed to participate in the proton-delivery, cascade, leading to dioxygen bond scission. This ferrous-dioxygen, structure suggests two classes of P450s based on the pathway of proton, transfer, one using the highly conserved threonine in the I-helix, (CYP101A1) and the other requiring hydroxyl groups of the substrate, molecules either directly transferring protons (CYP107A1) or stabilizing a, water pathway for proton transfer (CYP158A2).
About this Structure
2D0E is a Single protein structure of sequence from Bacteria with and as ligands. Full crystallographic information is available from OCA.
Reference
Role of active site water molecules and substrate hydroxyl groups in oxygen activation by cytochrome P450 158A2: a new mechanism of proton transfer., Zhao B, Guengerich FP, Voehler M, Waterman MR, J Biol Chem. 2005 Dec 23;280(51):42188-97. Epub 2005 Oct 20. PMID:16239228
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