Theoretical studies of the active-site structure, spectroscopic and thermodynamic properties, and reaction mechanism of multicopper oxidases

0391780 - ÚOCHB 2014 RIV NL eng J - Článek v odborném periodiku
Rulíšek, Lubomír - Ryde, U.
Theoretical studies of the active-site structure, spectroscopic and thermodynamic properties, and reaction mechanism of multicopper oxidases.
Coordination Chemistry Reviews. Roč. 257, č. 2 (2013), s. 445-458. ISSN 0010-8545. E-ISSN 1873-3840
Institucionální podpora: RVO:61388963
Klíčová slova: multi-copper oxidases * QM/MM calculations * multireference calculations * theoretical spectroscopy
Kód oboru RIV: CA - Anorganická chemie
Impakt faktor: 12.098, rok: 2013

In this article, we review recent theoretical work that has complemented the extensive experimental data available for the multicopper oxidases (MCO) and led to the elucidation of the reaction mechanism of this class of enzymes. The MCOs couple four one-electron oxidations of substrates at the mononuclear type 1 copper (Cu-T1) site with the four-electron reduction of dioxygen at the trinuclear copper cluster (TNC). The TNC consists of three copper ions arranged in a unique triangular fashion. In its oxidised form and in some experimentally observed intermediates (the peroxy and native intermediates), this leads to a magnetic coupling of the unpaired electrons of the three copper ions, resulting in unusual spectroscopic features. By correlating experimental and theoretical data, an unambiguous mapping between the structural, energetic and spectroscopic properties of the various intermediates in the MCO reaction cycle can be established. In terms of theory, these studies involved quantum mechanics (QM; density-functional theory and multi-reference self-consistent field) calculations, combined QM and molecular mechanics (QM/MM) modelling, ranging from standard QM/MM optimisations to the combination of QM/MM optimisation with EXAFS spectroscopy and QM/MM free-energy perturbations to accurately address phenomena such as the Cu-T1 -> TNC electron transfer, as well as the reduction potentials and acid constants of all the putative intermediates in the MCO reaction cycle. In summary, we try to demonstrate in this review that the MCOs are not only an attractive playground for theoretical methods, but the results of the calculations (when carefully correlated with and benchmarked against experimental data) can also be used to draw unambiguous conclusions about MCO structure and reactivity.
Trvalý link: http://hdl.handle.net/11104/0220753