2d09

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{{STRUCTURE_2d09| PDB=2d09 | SCENE= }}
{{STRUCTURE_2d09| PDB=2d09 | SCENE= }}
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'''A Role for Active Site Water Molecules and Hydroxyl Groups of Substrate for Oxygen Activation in Cytochrome P450 158A2'''
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===A Role for Active Site Water Molecules and Hydroxyl Groups of Substrate for Oxygen Activation in Cytochrome P450 158A2===
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==Overview==
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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).
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{{ABSTRACT_PUBMED_16239228}}
==About this Structure==
==About this Structure==
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==Reference==
==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:[http://www.ncbi.nlm.nih.gov/pubmed/16239228 16239228]
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:[http://www.ncbi.nlm.nih.gov/pubmed/16239228 16239228]
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Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2., Zhao B, Guengerich FP, Bellamine A, Lamb DC, Izumikawa M, Lei L, Podust LM, Sundaramoorthy M, Kalaitzis JA, Reddy LM, Kelly SL, Moore BS, Stec D, Voehler M, Falck JR, Shimada T, Waterman MR, J Biol Chem. 2005 Mar 25;280(12):11599-607. Epub 2005 Jan 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15659395 15659395]
[[Category: Bacteria]]
[[Category: Bacteria]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Proton transfer]]
[[Category: Proton transfer]]
[[Category: Streptomyce]]
[[Category: Streptomyce]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 23:27:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:19:34 2008''

Revision as of 09:19, 28 July 2008

Image:2d09.png

Template:STRUCTURE 2d09

A Role for Active Site Water Molecules and Hydroxyl Groups of Substrate for Oxygen Activation in Cytochrome P450 158A2

Template:ABSTRACT PUBMED 16239228

About this Structure

2D09 is a Single protein structure of sequence from Bacteria. 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

Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2., Zhao B, Guengerich FP, Bellamine A, Lamb DC, Izumikawa M, Lei L, Podust LM, Sundaramoorthy M, Kalaitzis JA, Reddy LM, Kelly SL, Moore BS, Stec D, Voehler M, Falck JR, Shimada T, Waterman MR, J Biol Chem. 2005 Mar 25;280(12):11599-607. Epub 2005 Jan 19. PMID:15659395

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