Please use this identifier to cite or link to this item:
Title: Redox-Linked Domain Movements in the Catalytic Cycle of Cytochrome P450 Reductase
Authors: Huang, Wei-Cheng
Ellis, Jacqueline
Moody, Peter C.E.
Raven, Emma L.
Roberts, Gordon C.K.
First Published: 1-Aug-2013
Publisher: Elsevier (Cell Press)
Citation: Structure, 2013, 21 (9), pp. 1581-1589
Abstract: NADPH-cytochrome P450 reductase is a key component of the P450 mono-oxygenase drug-metabolizing system. There is evidence for a conformational equilibrium involving large-scale domain motions in this enzyme. We now show, using small-angle X-ray scattering (SAXS) and small-angle neutron scattering, that delivery of two electrons to cytochrome P450 reductase leads to a shift in this equilibrium from a compact form, similar to the crystal structure, toward an extended form, while coenzyme binding favors the compact form. We present a model for the extended form of the enzyme based on nuclear magnetic resonance and SAXS data. Using the effects of changes in solution conditions and of site-directed mutagenesis, we demonstrate that the conversion to the extended form leads to an enhanced ability to transfer electrons to cytochrome c. This structural evidence shows that domain motion is linked closely to the individual steps of the catalytic cycle of cytochrome P450 reductase, and we propose a mechanism for this.
DOI Link: 10.1016/j.str.2013.06.022
ISSN: 0969-2126
eISSN: 1878-4186
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2013. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Biochemistry

Files in This Item:
File Description SizeFormat 
1-s2.0-S0969212613002463-main.pdfPublished (publisher PDF)1.87 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.