Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase

Bojana Ginovska-Pangovska, Ming Hsun Ho, John Linehan, Yuhui Cheng, Michel Dupuis, Simone Raugei, Wendy J. Shaw

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Possible proton transport pathways in Clostridium pasteurianum (CpI) [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to evaluate the functional pathway and provide insight into the hydrogen bonding features defining an active proton transport pathway. Three pathways were evaluated, two of which consist of water wires and one of predominantly amino acid residues. Our simulations suggest that protons are not transported through water wires. Instead, the five-residue motif (Glu282, Ser319, Glu279, H2O, Cys299) was found to be the likely pathway, consistent with previously made experimental observations. The pathway was found to have a persistent hydrogen bonded core (residues Cys299 to Ser319), with less persistent hydrogen bonds at the ends of the pathway for both H2 release and H2 uptake. Single site mutations of the four residues have been shown experimentally to deactivate the enzyme. The theoretical evaluation of these mutations demonstrates redistribution of the hydrogen bonds in the pathway, resulting in enzyme deactivation. Finally, coupling between the protein dynamics near the proton transport pathway and the redox partner binding regions was also found as a function of H2 uptake and H2 release states, which may be indicative of a correlation between proton and electron movement within the enzyme.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1837
Issue number1
DOIs
Publication statusPublished - 2014

Fingerprint

Hydrogenase
Molecular Dynamics Simulation
Molecular dynamics
Protons
Hydrogen
Hydrogen bonds
Enzymes
Wire
Clostridium
Mutation
Water
Active Biological Transport
Hydrogen Bonding
Oxidation-Reduction
Electrons
Amino Acids
Computer simulation
Proteins

Keywords

  • [FeFe]-hydrogenase
  • Hydrogen bonding
  • Molecular dynamics
  • Mutations
  • Proton transport

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase. / Ginovska-Pangovska, Bojana; Ho, Ming Hsun; Linehan, John; Cheng, Yuhui; Dupuis, Michel; Raugei, Simone; Shaw, Wendy J.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1837, No. 1, 2014, p. 131-138.

Research output: Contribution to journalArticle

Ginovska-Pangovska, Bojana ; Ho, Ming Hsun ; Linehan, John ; Cheng, Yuhui ; Dupuis, Michel ; Raugei, Simone ; Shaw, Wendy J. / Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase. In: Biochimica et Biophysica Acta - Bioenergetics. 2014 ; Vol. 1837, No. 1. pp. 131-138.
@article{c946e4fd34e340729c7ff2d6bac94617,
title = "Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase",
abstract = "Possible proton transport pathways in Clostridium pasteurianum (CpI) [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to evaluate the functional pathway and provide insight into the hydrogen bonding features defining an active proton transport pathway. Three pathways were evaluated, two of which consist of water wires and one of predominantly amino acid residues. Our simulations suggest that protons are not transported through water wires. Instead, the five-residue motif (Glu282, Ser319, Glu279, H2O, Cys299) was found to be the likely pathway, consistent with previously made experimental observations. The pathway was found to have a persistent hydrogen bonded core (residues Cys299 to Ser319), with less persistent hydrogen bonds at the ends of the pathway for both H2 release and H2 uptake. Single site mutations of the four residues have been shown experimentally to deactivate the enzyme. The theoretical evaluation of these mutations demonstrates redistribution of the hydrogen bonds in the pathway, resulting in enzyme deactivation. Finally, coupling between the protein dynamics near the proton transport pathway and the redox partner binding regions was also found as a function of H2 uptake and H2 release states, which may be indicative of a correlation between proton and electron movement within the enzyme.",
keywords = "[FeFe]-hydrogenase, Hydrogen bonding, Molecular dynamics, Mutations, Proton transport",
author = "Bojana Ginovska-Pangovska and Ho, {Ming Hsun} and John Linehan and Yuhui Cheng and Michel Dupuis and Simone Raugei and Shaw, {Wendy J.}",
year = "2014",
doi = "10.1016/j.bbabio.2013.08.004",
language = "English",
volume = "1837",
pages = "131--138",
journal = "Biochimica et Biophysica Acta - Bioenergetics",
issn = "0005-2728",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Molecular dynamics study of the proposed proton transport pathways in [FeFe]-hydrogenase

AU - Ginovska-Pangovska, Bojana

AU - Ho, Ming Hsun

AU - Linehan, John

AU - Cheng, Yuhui

AU - Dupuis, Michel

AU - Raugei, Simone

AU - Shaw, Wendy J.

PY - 2014

Y1 - 2014

N2 - Possible proton transport pathways in Clostridium pasteurianum (CpI) [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to evaluate the functional pathway and provide insight into the hydrogen bonding features defining an active proton transport pathway. Three pathways were evaluated, two of which consist of water wires and one of predominantly amino acid residues. Our simulations suggest that protons are not transported through water wires. Instead, the five-residue motif (Glu282, Ser319, Glu279, H2O, Cys299) was found to be the likely pathway, consistent with previously made experimental observations. The pathway was found to have a persistent hydrogen bonded core (residues Cys299 to Ser319), with less persistent hydrogen bonds at the ends of the pathway for both H2 release and H2 uptake. Single site mutations of the four residues have been shown experimentally to deactivate the enzyme. The theoretical evaluation of these mutations demonstrates redistribution of the hydrogen bonds in the pathway, resulting in enzyme deactivation. Finally, coupling between the protein dynamics near the proton transport pathway and the redox partner binding regions was also found as a function of H2 uptake and H2 release states, which may be indicative of a correlation between proton and electron movement within the enzyme.

AB - Possible proton transport pathways in Clostridium pasteurianum (CpI) [FeFe]-hydrogenase were investigated with molecular dynamics simulations. This study was undertaken to evaluate the functional pathway and provide insight into the hydrogen bonding features defining an active proton transport pathway. Three pathways were evaluated, two of which consist of water wires and one of predominantly amino acid residues. Our simulations suggest that protons are not transported through water wires. Instead, the five-residue motif (Glu282, Ser319, Glu279, H2O, Cys299) was found to be the likely pathway, consistent with previously made experimental observations. The pathway was found to have a persistent hydrogen bonded core (residues Cys299 to Ser319), with less persistent hydrogen bonds at the ends of the pathway for both H2 release and H2 uptake. Single site mutations of the four residues have been shown experimentally to deactivate the enzyme. The theoretical evaluation of these mutations demonstrates redistribution of the hydrogen bonds in the pathway, resulting in enzyme deactivation. Finally, coupling between the protein dynamics near the proton transport pathway and the redox partner binding regions was also found as a function of H2 uptake and H2 release states, which may be indicative of a correlation between proton and electron movement within the enzyme.

KW - [FeFe]-hydrogenase

KW - Hydrogen bonding

KW - Molecular dynamics

KW - Mutations

KW - Proton transport

UR - http://www.scopus.com/inward/record.url?scp=84884756810&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884756810&partnerID=8YFLogxK

U2 - 10.1016/j.bbabio.2013.08.004

DO - 10.1016/j.bbabio.2013.08.004

M3 - Article

C2 - 23981729

AN - SCOPUS:84884756810

VL - 1837

SP - 131

EP - 138

JO - Biochimica et Biophysica Acta - Bioenergetics

JF - Biochimica et Biophysica Acta - Bioenergetics

SN - 0005-2728

IS - 1

ER -