Water-assisted Proton Transfer in 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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Proton transfer in Azotobacter vinelandii ferredoxin I: entatic Lys84 operates as elastic counterbalance for the proton-carrying Asp15

Biochimica et Biophysica Acta (BBA) - Bioenergetics ◽

10.1016/s0005-2728(01)00162-1 ◽

2001 ◽

Vol 1505 (2-3) ◽

pp. 179-184 ◽

Cited By ~ 6

Author(s):

Dmitry A. Cherepanov ◽

Armen Y. Mulkidjanian

Keyword(s):

Proton Transfer ◽

Azotobacter Vinelandii ◽

Ferredoxin I

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Azotobacter vinelandii ferredoxin I: Aspartate-15 facilitates proton transfer to the [3Fe4S]0 cluster

Journal of Inorganic Biochemistry ◽

10.1016/0162-0134(93)85086-n ◽

1993 ◽

Vol 51 (1-2) ◽

pp. 48

Author(s):

B.K. Burgess ◽

B. Shen ◽

L.L. Martin ◽

J.N. Butt ◽

F.A. Armstrong ◽

...

Keyword(s):

Proton Transfer ◽

Azotobacter Vinelandii ◽

Ferredoxin I

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Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1409543112 ◽

2015 ◽

Vol 112 (7) ◽

pp. 2040-2045 ◽

Cited By ~ 45

Author(s):

Vivek Sharma ◽

Giray Enkavi ◽

Ilpo Vattulainen ◽

Tomasz Róg ◽

Mårten Wikström

Keyword(s):

Electron Transfer ◽

Free Energy ◽

Proton Transfer ◽

Short Circuit ◽

Proton Pumping ◽

Free Energy Calculations ◽

Water Molecules ◽

Transfer Event ◽

Proton Coupled Electron Transfer ◽

Dynamics Simulations

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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Supramolecular association in proton-transfer adducts containing benzamidinium cations. III. Three molecular salts of 3-methoxy-, 4-methoxy- and 3,4,5-trimethoxybenzoates with benzamidine

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229614001090 ◽

2014 ◽

Vol 70 (2) ◽

pp. 225-229 ◽

Cited By ~ 1

Author(s):

Gustavo Portalone

Keyword(s):

Proton Transfer ◽

Salt Bridge ◽

Transfer Reactions ◽

Water Molecules ◽

Asymmetric Unit ◽

Carboxylate Groups ◽

Molecular Salts ◽

Proton Transfer Reactions ◽

Molecular Components ◽

Molecular Salt

Three molecular salts, benzamidinium 3-methoxybenzoate, C7H9N2+·C8H7O3−, (I), benzamidinium 4-methoxybenzoate, C7H9N2+·C8H7O3−, (II), and benzamidinium 3,4,5-trimethoxybenzoate monohydrate, C7H9N2+·C10H11O5−·H2O, (III), were formed from the proton-transfer reactions of 3-methoxy, 4-methoxy- and 3,4,5-trimethoxybenzoic acids with benzamidine (benzenecarboximidamide, benzam). Monoclinic salts (I) and (II) have a 1:1 ratio of cation to anion. In monoclinic salt (III), two cation–anion pairs and two water molecules constitute the asymmetric unit. In all three molecular salts, the amidinium fragments and the carboxylate groups are completely delocalized, and the delocalization favours the aggregation of the molecular components into nonplanar dimers with anR22(8) graph-set motif by N+—H...O−(±) charge-assisted hydrogen bonding (CAHB). Of the three molecular salts, (I) and (II) show similar conformations of the anionic components and exhibit bidimensional isostructurality, which consists of alternatingR22(8) andR46(16) rings resulting in a corrugated sheet propagated parallel to the crystallographicabplane. In molecular salt (III), theR22(8) synthon is retained but the supramolecular structure is different, due to the presence of three bulky methoxy substituents and a water molecule. The structures reported here further demonstrate the robustness ofR22(8) hydrogen-bonded synthons having the benzamidinium cation as a building block, whereas N+—H...O−hydrogen bonds external to the salt bridge contribute to the overall structure organization.

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