期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：16
页码：6585-6590
DOI：10.1073/pnas.0902127106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The coupled binuclear "type 3" Cu sites are found in hemocyanin (Hc), tyrosinase (Tyr), and the multicopper oxidases (MCOs), such as laccase (Lc), and play vital roles in O2 respiration. Although all type 3 Cu sites share the same ground state features, those of Hc/Tyr have very different ligand-binding properties relative to those of the MCOs. In particular, the type 3 Cu site in the MCOs (LcT3) is a part of the trinuclear Cu cluster, and if the third (i.e., type 2) Cu is removed, the LcT3 site does not react with O2. Density functional theory calculations indicate that O2 binding in Hc is {approx}9 kcal mol-1 more favorable than for LcT3. The difference is mostly found in the total energy difference of the deoxy states ({approx}7 kcal mol-1), where the stabilization of deoxy LcT3 derives from its long equilibrium Cu-Cu distance of {approx}5.5-6.5 A, relative to {approx}4.2 A in deoxy Hc/Tyr. The O2 binding in Hc is driven by the electrostatic destabilization of the deoxy Hc site, in which the two Cu(I) centers are kept close together by the protein for facile 2-electron reduction of O2. Alternatively, the lack of O2 reactivity in LcT3 reflects the flexibility of the active site, capable of minimizing the electrostatic repulsion of the 2 Cu(I)s. Thus, the O2 reactivity of the MCOs is intrinsic to the trinuclear Cu cluster, leading to different O2 intermediates as required by its function of irreversible reduction of O2 to H2O.
