Energy landscapes and catalysis in nitric-oxide synthase

Anna Sobolewska-Stawiarz; Nicole G H Leferink; Karl Fisher; Derren J. Heyes; Sam Hay; Stephen E J Rigby; Nigel S. Scrutton

doi:10.1074/jbc.M114.548834

Energy landscapes and catalysis in nitric-oxide synthase

Anna Sobolewska-Stawiarz
, Nicole G H Leferink
, Karl Fisher
, Derren J. Heyes
, Sam Hay
, Stephen E J Rigby
, Nigel S. Scrutton

Chemical Biology and Biological Chemistry

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

Abstract

Background: Protein domain dynamics and calmodulin binding are implicated in regulating electron flow in NO synthase. Results: A dynamic conformational landscape important for enzyme catalysis is demonstrated. Conclusion:NOsynthesis requires a complex landscape of conformations, with calmodulin as a key driver of chemistry through modulation of the dynamic landscape. Significance: Detailed understanding of conformational landscapes provides new opportunities for inhibitor discovery targeted at the dynamic interfaces. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Original language	English
Pages (from-to)	11725-11738
Number of pages	13
Journal	Journal of Biological Chemistry
Volume	289
Issue number	17
DOIs	https://doi.org/10.1074/jbc.M114.548834
Publication status	Published - 25 Apr 2014

Keywords

Calmodulin
Enzyme Kinetics
Flavoproteins
Free Energy Landscapes
High Pressure Stopped Flow
Nitric-oxide Synthase
PELDOR Spectroscopy
Protein Dynamics

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10.1074/jbc.M114.548834Licence: CC BY

http://www.jbc.org/content/289/17/11725.full.pdf+html

Linking experiment to theory: Quantum entanglement during enzyme catalysis - Dr S Hay fellowship
Hay, S. (PI)
1/09/10 → 31/08/15
Project: Research

Cite this

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title = "Energy landscapes and catalysis in nitric-oxide synthase",

abstract = "Background: Protein domain dynamics and calmodulin binding are implicated in regulating electron flow in NO synthase. Results: A dynamic conformational landscape important for enzyme catalysis is demonstrated. Conclusion:NOsynthesis requires a complex landscape of conformations, with calmodulin as a key driver of chemistry through modulation of the dynamic landscape. Significance: Detailed understanding of conformational landscapes provides new opportunities for inhibitor discovery targeted at the dynamic interfaces. {\textcopyright} 2014 by The American Society for Biochemistry and Molecular Biology, Inc.",

keywords = "Calmodulin, Enzyme Kinetics, Flavoproteins, Free Energy Landscapes, High Pressure Stopped Flow, Nitric-oxide Synthase, PELDOR Spectroscopy, Protein Dynamics",

author = "Anna Sobolewska-Stawiarz and Leferink, \{Nicole G H\} and Karl Fisher and Heyes, \{Derren J.\} and Sam Hay and Rigby, \{Stephen E J\} and Scrutton, \{Nigel S.\}",

year = "2014",

month = apr,

day = "25",

doi = "10.1074/jbc.M114.548834",

language = "English",

volume = "289",

pages = "11725--11738",

journal = "Journal of Biological Chemistry",

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T1 - Energy landscapes and catalysis in nitric-oxide synthase

AU - Sobolewska-Stawiarz, Anna

AU - Leferink, Nicole G H

AU - Fisher, Karl

AU - Heyes, Derren J.

AU - Hay, Sam

AU - Rigby, Stephen E J

AU - Scrutton, Nigel S.

PY - 2014/4/25

Y1 - 2014/4/25

N2 - Background: Protein domain dynamics and calmodulin binding are implicated in regulating electron flow in NO synthase. Results: A dynamic conformational landscape important for enzyme catalysis is demonstrated. Conclusion:NOsynthesis requires a complex landscape of conformations, with calmodulin as a key driver of chemistry through modulation of the dynamic landscape. Significance: Detailed understanding of conformational landscapes provides new opportunities for inhibitor discovery targeted at the dynamic interfaces. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

AB - Background: Protein domain dynamics and calmodulin binding are implicated in regulating electron flow in NO synthase. Results: A dynamic conformational landscape important for enzyme catalysis is demonstrated. Conclusion:NOsynthesis requires a complex landscape of conformations, with calmodulin as a key driver of chemistry through modulation of the dynamic landscape. Significance: Detailed understanding of conformational landscapes provides new opportunities for inhibitor discovery targeted at the dynamic interfaces. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

KW - Calmodulin

KW - Enzyme Kinetics

KW - Flavoproteins

KW - Free Energy Landscapes

KW - High Pressure Stopped Flow

KW - Nitric-oxide Synthase

KW - PELDOR Spectroscopy

KW - Protein Dynamics

U2 - 10.1074/jbc.M114.548834

DO - 10.1074/jbc.M114.548834

M3 - Article

C2 - 24610812

SN - 1083-351X

VL - 289

SP - 11725

EP - 11738

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 17

ER -

Energy landscapes and catalysis in nitric-oxide synthase

Abstract

Keywords

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Projects

Linking experiment to theory: Quantum entanglement during enzyme catalysis - Dr S Hay fellowship

Cite this