TUTCRIS Research Portal

TY - JOUR

T1 - Proton-coupled electron transfer and the role of water molecules in proton pumping by cytochrome c oxidase

AU - Sharma, V.

AU - Enkavi, G.

AU - Vattulainen, I.

AU - Róg, T.

AU - Wikström, M.

PY - 2015/2/17

Y1 - 2015/2/17

N2 - 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 redoxstate-dependent organization of water molecules within the protein structure that gates the proton transfer pathway. cell respiration , atomistic molecular dynamics simulations , functional water molecules ,free-energy calculations .

AB - 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 redoxstate-dependent organization of water molecules within the protein structure that gates the proton transfer pathway. cell respiration , atomistic molecular dynamics simulations , functional water molecules ,free-energy calculations .

UR - http://www.scopus.com/inward/record.url?scp=84923209928&partnerID=8YFLogxK

U2 - 10.1073/pnas.1409543112

DO - 10.1073/pnas.1409543112

M3 - Article

VL - 112

SP - 2040

EP - 2045

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 7

ER -