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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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

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