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Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase

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journal contribution
posted on 09.10.2017, 15:03 by Samuel L. Freeman, Anne Martel, Emma L. Raven, Gordon C. K. Roberts
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.

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Citation

Scientific Reports, 2017, 7 (1), Article number: 9741

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Old Departments Pre 01 Aug 2015/Department of Biochemistry (Pre 01 Aug 2015)

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VoR (Version of Record)

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Scientific Reports

Publisher

Nature Publishing Group

eissn

2045-2322

Acceptance date

31/07/2017

Copyright date

2017

Available date

09/10/2017

Publisher version

https://www.nature.com/articles/s41598-017-09840-8

Language

en

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