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 language | English |
|---|---|
| Pages (from-to) | 131-138 |
| Number of pages | 8 |
| Journal | Biochimica et Biophysica Acta - Bioenergetics |
| Volume | 1837 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2014 |
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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 journal › Article
}
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
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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
VL - 1837
SP - 131
EP - 138
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
SN - 0005-2728
IS - 1
ER -