Monte Carlo simulations of proton pumps: on the working principles of the biological valve that controls proton pumping in cytochrome c oxidase.

Proceedings of the National Academy of Sciences of the United States of America
Mats H M Olsson, Arieh Warshel

Abstract

Gaining a detailed understanding of the proton-pumping process in cytochrome c oxidase (COX) is one of the challenges of modern biophysics. Recent mutation experiments have highlighted this challenge by showing that a single mutation (the N139D mutation) blocks the overall pumping while continuing to channel protons to the binuclear center without inhibiting the oxidase activity. Rationalizing this result has been a major problem because the mutation is quite far from E286, which is believed to serve as the branching point for the proton transport in the pumping process. In the absence of a reasonable explanation for this important observation, we have developed a Monte Carlo simulation method that can convert mutation and structural information to pathways for proton translocation and simulate the pumping process in COX on a millisecond and even subsecond time scale. This tool allows us to reproduce and propose a possible explanation to the effect of the N139D mutation and to offer a consistent model for the origin of the "valve effect" in COX, which is crucial for maintaining uphill proton pumping. Furthermore, obtaining the first structure-based simulation of proton pumping in COX, or in any other protein, indicates that our...Continue Reading

References

Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·C OstermeierH Michel
Jun 12, 1998·Journal of Bioenergetics and Biomembranes·J J ReganB G Malmström
Jul 1, 1998·Annual Review of Biophysics and Biomolecular Structure·H MichelA Kannt
Nov 7, 1996·Chemical Reviews·Shelagh Ferguson-Miller, Gerald T. Babcock
Sep 11, 2002·Biochimica Et Biophysica Acta·Denise A Mills, Shelagh Ferguson-Miller
May 27, 2003·Biochimica Et Biophysica Acta·Mårten WikströmGerhard Hummer
Aug 9, 2003·Biochimica Et Biophysica Acta·Peter Brzezinski, Gisela Larsson
Mar 3, 2004·Biophysical Journal·Ming-Liang TanJosé Nelson Onuchic
May 29, 2004·FEBS Letters·Andreas Namslauer, Peter Brzezinski
Apr 9, 2005·Bioinformatics·Johan HattneJohan Elf
Apr 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jiancong Xu, Gregory A Voth
Jul 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Mårten WikströmAnne Puustinen
Sep 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·A Warshel, D W Schlosser
Jul 21, 2006·The Journal of Physical Chemistry. B·Dragan M PopovićAlexei A Stuchebrukhov

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Citations

Sep 4, 2013·Amino Acids·Dragan M Popović
Nov 1, 2008·Journal of Bioenergetics and Biomembranes·Peter Brzezinski, Robert B Gennis
Oct 3, 2008·Journal of Bioenergetics and Biomembranes·Martyn A Sharpe, Shelagh Ferguson-Miller
Nov 6, 2010·Chemical Reviews·Sharon Hammes-Schiffer, Alexei A Stuchebrukhov
Oct 23, 2010·Journal of the American Chemical Society·Hyun Ju LeeRobert B Gennis
Apr 14, 2007·The Journal of Physical Chemistry. B·Jessica M J SwansonGregory A Voth
Apr 29, 2011·Physical Chemistry Chemical Physics : PCCP·Shina Caroline Lynn Kamerlin, Arieh Warshel
May 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Andrei V PisliakovArieh Warshel
Apr 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ville R I KailaMårten Wikström
Feb 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Ida Namslauer, Peter Brzezinski
Apr 23, 2009·Proceedings of the National Academy of Sciences of the United States of America·Hanbin LiuArieh Warshel
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Young C KimGerhard Hummer
May 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ann-Louise JohanssonPeter Brzezinski
Jun 25, 2009·The Journal of Chemical Physics·Anatoly Yu SmirnovFranco Nori
Feb 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Young C KimGerhard Hummer
Nov 3, 2010·Annual Review of Physical Chemistry·Shina C L KamerlinArieh Warshel
Jan 7, 2014·FEBS Letters·Per E M Siegbahn, Margareta R A Blomberg
Jan 19, 2016·Biochimica Et Biophysica Acta·Gerhard Hummer, Mårten Wikström
Sep 24, 2015·Proceedings of the National Academy of Sciences of the United States of America·Raphael Alhadeff, Arieh Warshel
Sep 12, 2007·Proteins·Vitor H TeixeiraAntónio M Baptista
Apr 24, 2009·Biochimica Et Biophysica Acta·Ville R I KailaMårten Wiström
Aug 19, 2007·Biochimica Et Biophysica Acta·Per E M Siegbahn, Margareta R A Blomberg
Jul 18, 2006·Current Opinion in Structural Biology·Peter Brzezinski, Pia Adelroth
Aug 29, 2006·Biochimica Et Biophysica Acta·Colin A Wraight
Mar 20, 2013·Biochimica Et Biophysica Acta·M R GunnerJianxun Lu
Sep 29, 2011·Biochimica Et Biophysica Acta·Young C Kim, Gerhard Hummer
Dec 20, 2011·Biochimica Et Biophysica Acta·Yuxing Peng, Gregory A Voth
Nov 17, 2011·Biochimica Et Biophysica Acta·Dragan M Popović, Alexei A Stuchebrukhov
Apr 6, 2011·Biochimica Et Biophysica Acta·Ann-Louise JohanssonPeter Brzezinski
May 7, 2008·Biochimica Et Biophysica Acta·Håkan LeppPeter Brzezinski
Oct 8, 2011·Biochimica Et Biophysica Acta·Margareta R A Blomberg, Per E M Siegbahn
Mar 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Christoph von BallmoosPeter Brzezinski
Feb 27, 2010·Biochimica Et Biophysica Acta·Peter Brzezinski, Ann-Louise Johansson
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