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Quantum chemistry applied to the mechanisms of transition metal containing enzymes—Cytochrome c oxidase, a particularly challenging case
Author(s) -
Blomberg Margareta R. A.,
Siegbahn Per E. M.
Publication year - 2006
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20448
Subject(s) - exergonic reaction , cytochrome c oxidase , chemistry , active site , proton , catalytic cycle , redox , chemical physics , electron transport complex iv , density functional theory , cytochrome c , computational chemistry , catalysis , enzyme , physics , inorganic chemistry , quantum mechanics , mitochondrion , biochemistry
The Density functional theory (B3LYP) has been used to study the mechanisms of OO bond cleavage and proton pumping in cytochrome c oxidase. To understand how the energy from the exergonic reduction of molecular oxygen is used to pump protons across the mitochondrial membrane, the energetics of all steps in the catalytic cycle have to be evaluated. For this purpose, models have to be designed that can accurately reproduce relative redox potentials and pK a values within the active site. The present study shows that it is possible to construct such models and to calculate energy profiles which, to a large extent, agree with experimental information. However, the energy profiles point out a problem with an unbalanced partitioning of the energy between the reductive and oxidative half cycles, which is in disagreement with the experimental observation that the proton pumping is evenly distributed between the two half cycles. A conclusion from the present study is, therefore, that something is probably still missing in the modeling of the active site. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1373–1384, 2006