Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase

Samuel L. Freeman, Anne Martel, Emma L. Raven*, Gordon C.K. Roberts

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)
248 Downloads (Pure)

Abstract

NADPH-cytochrome P450 reductase is a multi-domain redox enzyme which is a key component of the P450 mono-oxygenase drug-metabolizing system. We report studies of the conformational equilibrium of this enzyme using small-angle neutron scattering, under conditions where we are able to control the redox state of the enzyme precisely. Different redox states have a profound effect on domain orientation in the enzyme and we analyse the data in terms of a two-state equilibrium between compact and extended conformations. The effects of ionic strength show that the presence of a greater proportion of the extended form leads to an enhanced ability to transfer electrons to cytochrome c. Domain motion is intrinsically linked to the functionality of the enzyme, and we can define the position of the conformational equilibrium for individual steps in the catalytic cycle.

Original languageEnglish
Article number9741
Number of pages11
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 29 Aug 2017

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