PMID- 26192749 OWN - NLM STAT- MEDLINE DCOM- 20160505 LR - 20231111 IS - 1520-510X (Electronic) IS - 0020-1669 (Print) IS - 0020-1669 (Linking) VI - 54 IP - 15 DP - 2015 Aug 3 TI - Broken Symmetry DFT Calculations/Analysis for Oxidized and Reduced Dinuclear Center in Cytochrome c Oxidase: Relating Structures, Protonation States, Energies, and Mossbauer Properties in ba3 Thermus thermophilus. PG - 7272-90 LID - 10.1021/acs.inorgchem.5b00700 [doi] AB - The Fea3(3+)...CuB(2+) dinuclear center (DNC) structure of the as-isolated oxidized ba3 cytochrome c oxidase (CcO) from Thermus thermophilus (Tt) is still not fully understood. When the proteins are initially crystallized in the oxidized state, they typically become radiolyticly reduced through X-ray irradiation. Several X-ray crystal structures of reduced ba3 CcO from Tt are available. However, depending on whether the crystals were prepared in a lipidic cubic phase environment or in detergent micelles, and whether the CcO's were chemically or radiolyticly reduced, the X-ray diffraction analysis of the crystals showed different Fea3(2+)...CuB(+) DNC structures. On the other hand, Mossbauer spectroscopic experiments on reduced and oxidized ba3 CcOs from Tt (Zimmermann et al., Proc. Natl. Acad. Sci. USA 1988, 85, 5779-5783) revealed multiple (57)Fea3(2+) and (57)Fea3(3+) components. Moreover, one of the (57)Fea3(3+) components observed at 4.2 K transformed from a proposed "low-spin" state to a different high-spin species when the temperature was increased above 190 K, whereas the other high-spin (57)Fea3(3+) component remained unchanged. In the current Article, in order to understand the heterogeneities of the DNC in both Mossbauer spectra and X-ray crystal structures, the spin crossover of one of the (57)Fea3(3+) components, and how the coordination and spin states of the Fea3(3+/2+) and Cu(2+/1+) sites relate to the heterogeneity of the DNC structures, we have applied density functional OLYP calculations to the DNC clusters established based on the different X-ray crystal structures of ba3 CcO from Tt. As a result, specific oxidized and reduced DNC structures related to the observed Mossbauer spectra and to spectral changes with temperature have been proposed. Our calculations also show that, in certain intermediate states, the His233 and His283 ligand side chains may dissociate from the CuB(+) site, and they may become potential proton loading sites during the catalytic cycle. FAU - Han Du, Wen-Ge AU - Han Du WG AD - Department of Integrative Structural and Computational Biology, CB213, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States. FAU - Noodleman, Louis AU - Noodleman L AD - Department of Integrative Structural and Computational Biology, CB213, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States. LA - eng GR - R01 GM100934/GM/NIGMS NIH HHS/United States GR - R01GM100934/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150720 PL - United States TA - Inorg Chem JT - Inorganic chemistry JID - 0366543 RN - 0 (Protons) RN - EC 1.9.3.1 (Electron Transport Complex IV) SB - IM MH - Animals MH - Cattle MH - Crystallography, X-Ray MH - Electron Transport Complex IV/*chemistry/*metabolism MH - Models, Molecular MH - Oxidation-Reduction MH - *Protons MH - *Quantum Theory MH - Spectroscopy, Mossbauer MH - Thermodynamics MH - Thermus thermophilus/*enzymology PMC - PMC4525772 EDAT- 2015/07/21 06:00 MHDA- 2016/05/06 06:00 PMCR- 2016/07/20 CRDT- 2015/07/21 06:00 PHST- 2015/07/21 06:00 [entrez] PHST- 2015/07/21 06:00 [pubmed] PHST- 2016/05/06 06:00 [medline] PHST- 2016/07/20 00:00 [pmc-release] AID - 10.1021/acs.inorgchem.5b00700 [doi] PST - ppublish SO - Inorg Chem. 2015 Aug 3;54(15):7272-90. doi: 10.1021/acs.inorgchem.5b00700. Epub 2015 Jul 20.