Key mutations alter the cytochrome P450 BM3 conformational landscape and remove inherent substrate bias

Christopher F. Butler; Caroline Peet; Amy E. Mason; Michael W. Voice; David Leys; Andrew W. Munro

doi:10.1074/jbc.M113.479717

Key mutations alter the cytochrome P450 BM3 conformational landscape and remove inherent substrate bias

Christopher F. Butler, Caroline Peet, Amy E. Mason, Michael W. Voice, David Leys, Andrew W. Munro

Research output: Contribution to journal › Article › peer-review

Abstract

Background: P450 BM3 is a high activity enzyme with biotechnological potential. Results: Mutations perturbing P450 BM3's conformational state and active site facilitate human P450-like oxidation of the drug omeprazole. Conclusion: Conformational destabilization enables P450 BM3 to explore novel conformations and accept diverse substrates. Significance: " Gatekeeper" mutations that decrease the energetic barrier for transition to the substrate-bound state can reconfigure P450 BM3 specificity and reactivity. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Original language	English
Pages (from-to)	25387-25399
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	288
Issue number	35
DOIs	https://doi.org/10.1074/jbc.M113.479717
Publication status	Published - 30 Aug 2013

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http://www.jbc.org/content/288/35/25387.full.pdf+html

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title = "Key mutations alter the cytochrome P450 BM3 conformational landscape and remove inherent substrate bias",

abstract = "Background: P450 BM3 is a high activity enzyme with biotechnological potential. Results: Mutations perturbing P450 BM3's conformational state and active site facilitate human P450-like oxidation of the drug omeprazole. Conclusion: Conformational destabilization enables P450 BM3 to explore novel conformations and accept diverse substrates. Significance: {"} Gatekeeper{"} mutations that decrease the energetic barrier for transition to the substrate-bound state can reconfigure P450 BM3 specificity and reactivity. {\textcopyright} 2013 by The American Society for Biochemistry and Molecular Biology, Inc.",

author = "Butler, {Christopher F.} and Caroline Peet and Mason, {Amy E.} and Voice, {Michael W.} and David Leys and Munro, {Andrew W.}",

year = "2013",

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doi = "10.1074/jbc.M113.479717",

language = "English",

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journal = "Journal of Biological Chemistry",

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TY - JOUR

T1 - Key mutations alter the cytochrome P450 BM3 conformational landscape and remove inherent substrate bias

AU - Butler, Christopher F.

AU - Peet, Caroline

AU - Mason, Amy E.

AU - Voice, Michael W.

AU - Leys, David

AU - Munro, Andrew W.

PY - 2013/8/30

Y1 - 2013/8/30

N2 - Background: P450 BM3 is a high activity enzyme with biotechnological potential. Results: Mutations perturbing P450 BM3's conformational state and active site facilitate human P450-like oxidation of the drug omeprazole. Conclusion: Conformational destabilization enables P450 BM3 to explore novel conformations and accept diverse substrates. Significance: " Gatekeeper" mutations that decrease the energetic barrier for transition to the substrate-bound state can reconfigure P450 BM3 specificity and reactivity. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

AB - Background: P450 BM3 is a high activity enzyme with biotechnological potential. Results: Mutations perturbing P450 BM3's conformational state and active site facilitate human P450-like oxidation of the drug omeprazole. Conclusion: Conformational destabilization enables P450 BM3 to explore novel conformations and accept diverse substrates. Significance: " Gatekeeper" mutations that decrease the energetic barrier for transition to the substrate-bound state can reconfigure P450 BM3 specificity and reactivity. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

U2 - 10.1074/jbc.M113.479717

DO - 10.1074/jbc.M113.479717

M3 - Article

SN - 1083-351X

VL - 288

SP - 25387

EP - 25399

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 35

ER -

Key mutations alter the cytochrome P450 BM3 conformational landscape and remove inherent substrate bias

Abstract

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