Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase

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

doi:10.1038/s41598-017-09840-8

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

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

24 Citations (Scopus)

284 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 language	English
Article number	9741
Number of pages	11
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/s41598-017-09840-8
Publication status	Published - 29 Aug 2017

Access to Document

10.1038/s41598-017-09840-8Licence: CC BY

Full-text PDF (final published version)
This is the final published version of the article (version of record). It first appeared online via Nature at https://doi.org/10.1038/s41598-017-09840-8. Please refer to any applicable terms of use of the publisher.
Final published version, 3.06 MBLicence: CC BY
Supplementary information PDF
This is the final published version of the article (version of record). It first appeared online via Nature at https://doi.org/10.1038/s41598-017-09840-8. Please refer to any applicable terms of use of the publisher.
Final published version, 404 KBLicence: CC BY

Handle.net

Persistent link

Cite this

@article{8f068cfd18284ef4a059397a49a73b95,

title = "Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase",

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.",

author = "Freeman, {Samuel L.} and Anne Martel and Raven, {Emma L.} and Roberts, {Gordon C.K.}",

year = "2017",

month = aug,

day = "29",

doi = "10.1038/s41598-017-09840-8",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Springer Nature",

}

TY - JOUR

T1 - Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase

AU - Freeman, Samuel L.

AU - Martel, Anne

AU - Raven, Emma L.

AU - Roberts, Gordon C.K.

PY - 2017/8/29

Y1 - 2017/8/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85028456565&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-09840-8

DO - 10.1038/s41598-017-09840-8

M3 - Article (Academic Journal)

C2 - 28852004

AN - SCOPUS:85028456565

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 9741

ER -

Orchestrated Domain Movement in Catalysis by Cytochrome P450 Reductase

Abstract

Access to Document

Handle.net

Other files and links

Fingerprint

Cite this