Water Molecules in Short- and Long-Distance Proton Transfer Steps of Bacteriorhodopsin Proton Pumping

Molecular oxygen acts as the terminal electron sink in the respiratory chains of aerobic organisms. Cytochrome c oxidase in the inner membrane of mitochondria and the plasma membrane of bacteria catalyzes the reduction of oxygen to water, and couples the free energy of the reaction to proton pumping across the membrane. The proton-pumping activity contributes to the proton electrochemical gradient, which drives the synthesis of ATP. Based on kinetic experiments on the O–O bond splitting transition of the catalytic cycle (A → PR), it has been proposed that the electron transfer to the binuclear iron–copper center of O2 reduction initiates the proton pump mechanism. This key electron transfer event is coupled to an internal proton transfer from a conserved glutamic acid to the proton-loading site of the pump. However, the proton may instead be transferred to the binuclear center to complete the oxygen reduction chemistry, which would constitute a short-circuit. Based on atomistic molecular dynamics simulations of cytochrome c oxidase in an explicit membrane–solvent environment, complemented by related free-energy calculations, we propose that this short-circuit is effectively prevented by a redox-state–dependent organization of water molecules within the protein structure that gates the proton transfer pathway.

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Water-assisted Proton Transfer in Ferredoxin I

Journal of Biological Chemistry ◽

10.1074/jbc.m111.230003 ◽

2011 ◽

Vol 286 (27) ◽

pp. 23679-23687 ◽

Cited By ~ 13

Author(s):

Stephan Lutz ◽

Ivan Tubert-Brohman ◽

Yonggang Yang ◽

Markus Meuwly

Keyword(s):

Proton Transfer ◽

Azotobacter Vinelandii ◽

Energy Difference ◽

Umbrella Sampling ◽

Proton Pumping ◽

Water Molecules ◽

Forward Reaction ◽

Proton Relay ◽

Proton Transfer Reactions ◽

Ferredoxin I

The role of water molecules in assisting proton transfer (PT) is investigated for the proton-pumping protein ferredoxin I (FdI) from Azotobacter vinelandii. It was shown previously that individual water molecules can stabilize between Asp15 and the buried [3Fe-4S]0 cluster and thus can potentially act as a proton relay in transferring H+ from the protein to the μ2 sulfur atom. Here, we generalize molecular mechanics with proton transfer to studying proton transfer reactions in the condensed phase. Both umbrella sampling simulations and electronic structure calculations suggest that the PT Asp15-COOH + H2O + [3Fe-4S]0 → Asp15-COO− + H2O + [3Fe-4S]0 H+ is concerted, and no stable intermediate hydronium ion (H3O+) is expected. The free energy difference of 11.7 kcal/mol for the forward reaction is in good agreement with the experimental value (13.3 kcal/mol). For the reverse reaction (Asp15-COO− + H2O + [3Fe-4S]0H+ → Asp15-COOH + H2O + [3Fe-4S]0), a larger barrier than for the forward reaction is correctly predicted, but it is quantitatively overestimated (23.1 kcal/mol from simulations versus 14.1 from experiment). Possible reasons for this discrepancy are discussed. Compared with the water-assisted process (ΔE ≈ 10 kcal/mol), water-unassisted proton transfer yields a considerably higher barrier of ΔE ≈ 35 kcal/mol.

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Faculty Opinions recommendation of Long-distance proton transfer with a break in the bacteriorhodopsin active site.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1161768.623370 ◽

2009 ◽

Author(s):

Qiang Cui

Keyword(s):

Proton Transfer ◽

Active Site ◽

Long Distance

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Proton Transfer in Bulk Water using the Full Adaptive QM/MM Method: Integration of Solute- and Solvent-Adaptive Approaches

10.26434/chemrxiv.12638285 ◽

2020 ◽

Author(s):

Hiroshi C. Watanabe ◽

Masayuki Yamada ◽

Yohichi Suzuki

Keyword(s):

Proton Transfer ◽

Control Algorithm ◽

Adaptive Methods ◽

Bulk Water ◽

Water Molecules ◽

Adaptive Treatment ◽

Grotthuss Mechanism ◽

Hydronium Ions ◽

Method Integration ◽

Large Systems

<div><div>The quantum mechanical/molecular mechanical (QM/MM) method is a hybrid molecular simulation technique that increases the accessibility of local electronic structures of large systems.</div><div> The technique combines the benefit of accuracy found in the QM method and that of cost efficiency found in the MM method.</div><div> However, it is difficult to directly apply the QM/MM method to the dynamics of solution systems, particularly for proton transfer. </div><div> As explained in the Grotthuss mechanism, proton transfer is a structural interconversion between hydronium ions and solvent water molecules. </div><div> Hence, when the QM/MM method is applied, an adaptive treatment, namely on-the-fly revisions on molecular definitions, is required for both the solute and solvent. </div><div> Although several solvent-adaptive methods have been proposed, a full adaptive framework, which is an approach that also considers adaptation for solutes, remains untapped. In this paper, we propose a new numerical expression for the coordinates of the excess proton and its control algorithm.</div><div> Furthermore, we confirm that this method can stably and accurately simulate proton transfer dynamics in bulk water.</div></div>

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Crystal structure and hydrogen bonding in the water-stabilized proton-transfer salt brucinium 4-aminophenylarsonate tetrahydrate

Acta Crystallographica Section E Crystallographic Communications ◽

10.1107/s2056989016006691 ◽

2016 ◽

Vol 72 (5) ◽

pp. 751-755 ◽

Cited By ~ 1

Author(s):

Graham Smith ◽

Urs D. Wermuth

Keyword(s):

Crystal Structure ◽

Hydrogen Bond ◽

Hydrogen Bonding ◽

Hydrogen Bonds ◽

Proton Transfer ◽

Network Structure ◽

Three Dimensional ◽

Water Molecules ◽

Arsanilic Acid ◽

Dimensional Network

In the structure of the brucinium salt of 4-aminophenylarsonic acid (p-arsanilic acid), systematically 2,3-dimethoxy-10-oxostrychnidinium 4-aminophenylarsonate tetrahydrate, (C23H27N2O4)[As(C6H7N)O2(OH)]·4H2O, the brucinium cations form the characteristic undulating and overlapping head-to-tail layered brucine substructures packed along [010]. The arsanilate anions and the water molecules of solvation are accommodated between the layers and are linked to them through a primary cation N—H...O(anion) hydrogen bond, as well as through water O—H...O hydrogen bonds to brucinium and arsanilate ions as well as bridging water O-atom acceptors, giving an overall three-dimensional network structure.

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Ion-water coupling controls class A GPCR signal transduction pathways

10.1101/2020.08.28.271510 ◽

2020 ◽

Author(s):

Neil J. Thomson ◽

Owen N. Vickery ◽

Callum M. Ives ◽

Ulrich Zachariae

Keyword(s):

Binding Site ◽

G Protein ◽

Signal Transmission ◽

Water Molecules ◽

Long Distance ◽

Protein Binding Region ◽

Dynamics Simulations ◽

Key Residues ◽

Extracellular Sodium ◽

Communication Pathway

G-protein-coupled receptors (GPCRs) transmit signals across the cell membrane, forming the largest family of membrane proteins in humans. Most GPCRs activate through an evolutionarily conserved mechanism, which involves reorientation of helices and key residues, rearrangement of a hydrogen bonding network mediated by water molecules, and the expulsion of a sodium ion from a protonatable binding site. However, how these components interplay to engage the signal effector binding site remains elusive. Here, we applied information theory to molecular dynamics simulations of pharmaceutically important GPCRs to trace concerted conformational variations across the receptors. We discovered a conserved communication pathway that includes protein residues and cofactors and enables the exchange of information between the extracellular sodium binding site and the intracellular G-protein binding region, coupling the most highly conserved protonatable residues at long distance. Reorientation of internal water molecules was found to be essential for signal transmission along this pathway. By inhibiting protonation, sodium decoupled this connectivity, identifying the ion as a master switch that determines the receptors’ ability to move towards active conformations.

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Validity and limitations of simple reaction kinetics to calculate concentrations of organic compounds from ion counts in PTR-MS

Atmospheric Measurement Techniques ◽

10.5194/amt-12-6193-2019 ◽

2019 ◽

Vol 12 (11) ◽

pp. 6193-6208 ◽

Cited By ~ 7

Author(s):

Rupert Holzinger ◽

W. Joe F. Acton ◽

William J. Bloss ◽

Martin Breitenlechner ◽

Leigh R. Crilley ◽

...

Keyword(s):

Proton Transfer ◽

Reaction Kinetics ◽

Transfer Reaction ◽

Performance Status ◽

Calibration Method ◽

Proton Transfer Reaction ◽

Rural Site ◽

Water Molecules ◽

Simple Reaction ◽

Wide Range

Abstract. In September 2017, we conducted a proton-transfer-reaction mass-spectrometry (PTR-MS) intercomparison campaign at the CESAR observatory, a rural site in the central Netherlands near the village of Cabauw. Nine research groups deployed a total of 11 instruments covering a wide range of instrument types and performance. We applied a new calibration method based on fast injection of a gas standard through a sample loop. This approach allows calibrations on timescales of seconds, and within a few minutes an automated sequence can be run allowing one to retrieve diagnostic parameters that indicate the performance status. We developed a method to retrieve the mass-dependent transmission from the fast calibrations, which is an essential characteristic of PTR-MS instruments, limiting the potential to calculate concentrations based on counting statistics and simple reaction kinetics in the reactor/drift tube. Our measurements show that PTR-MS instruments follow the simple reaction kinetics if operated in the standard range for pressures and temperature of the reaction chamber (i.e. 1–4 mbar, 30–120∘, respectively), as well as a reduced field strength E∕N in the range of 100–160 Td. If artefacts can be ruled out, it becomes possible to quantify the signals of uncalibrated organics with accuracies better than ±30 %. The simple reaction kinetics approach produces less accurate results at E∕N levels below 100 Td, because significant fractions of primary ions form water hydronium clusters. Deprotonation through reactive collisions of protonated organics with water molecules needs to be considered when the collision energy is a substantial fraction of the exoergicity of the proton transfer reaction and/or if protonated organics undergo many collisions with water molecules.

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Rigidly hydrogen-bonded water molecules facilitate proton transfer in photosystem II

Physical Chemistry Chemical Physics ◽

10.1039/d0cp00295j ◽

2020 ◽

Vol 22 (28) ◽

pp. 15831-15841

Author(s):

Naoki Sakashita ◽

Hiroshi Ishikita ◽

Keisuke Saito

Keyword(s):

Photosystem Ii ◽

Proton Transfer ◽

Water Molecules ◽

Hydrogen Bonded

In the channel of photosystem II, rigidly hydrogen-bonded water molecules facilitate the Grotthuss-like proton transfer, whereas flexible water molecules prevent proton transfer in the channel of aquaporin.

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Calculation of the proton transfer between water molecules

Chemical Physics Letters ◽

10.1016/0009-2614(70)80147-6 ◽

1970 ◽

Vol 6 (2) ◽

pp. 117-120 ◽

Cited By ~ 7

Author(s):

Yeong Fang ◽

Jose R. De La Vega

Keyword(s):

Proton Transfer ◽

Water Molecules

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Microscopic basis for kinetic gating in cytochrome c oxidase: insights from QM/MM analysis

Chemical Science ◽

10.1039/c4sc01674b ◽

2015 ◽

Vol 6 (1) ◽

pp. 826-841 ◽

Cited By ~ 27

Author(s):

Puja Goyal ◽

Shuo Yang ◽

Qiang Cui

Keyword(s):

Cytochrome C ◽

Proton Transfer ◽

Cytochrome C Oxidase ◽

Proton Pumping ◽

Kinetic Features

Understanding the mechanism of vectorial proton pumping in biomolecules requires establishing the microscopic basis for the regulation of both thermodynamic and kinetic features of the relevant proton transfer steps.

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