The mechanism for proton pumping in cytochrome c oxidase from an electrostatic and quantum chemical perspective
2012 (English)In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1817, no 4, 495-505 p.Article, review/survey (Refereed) Published
The mechanism for proton pumping in cytochrome c oxidase in the respiratory chain, has for decades been one of the main unsolved problems in biochemistry. However, even though several different suggested mechanisms exist, many of the steps in these mechanisms are quite similar and constitute a general consensus framework for discussing proton pumping. When these steps are analyzed, at least three critical gating situations are found, and these points are where the suggested mechanisms in general differ. The requirements for gating are reviewed and analyzed in detail, and a mechanism is suggested, where solutions for all the gating situations are formulated. This mechanism is based on an electrostatic analysis of a kinetic experiment for the O to E transition. The key component of the mechanism is a positively charged transition state. An electron on heme a opens the gate for proton transfer from the N-side to a pump loading site (PLS). When the negative charge of the electron is compensated by a chemical proton, the positive transition state prevents backflow from the PLS to the N-side at the most critical stage of the pumping process. The mechanism has now been tested by large model DFT calculations, and these calculations give strong support for the suggested mechanism. This article is part of a Special Issue entitled: Respiratory Oxidases.
Place, publisher, year, edition, pages
2012. Vol. 1817, no 4, 495-505 p.
Cytochrome c oxidase, Proton pumping, Gating, Quantum chemistry, DFT
IdentifiersURN: urn:nbn:se:su:diva-76047DOI: 10.1016/j.bbabio.2011.09.014ISI: 000301885600005OAI: oai:DiVA.org:su-76047DiVA: diva2:525792