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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
43
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pubmed:dateCreated |
2007-10-24
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pubmed:abstractText |
The multicopper oxidases (MCOs) utilize a blue type 1 (T1) copper site and a trinuclear Cu cluster composed of a type 2 (T2) and a binuclear type 3 (T3) site that together catalyze the four-electron reduction of O2 to H2O. Reaction of the fully reduced enzyme with O2 proceeds via two sequential two-electron steps generating the peroxy intermediate (PI) and the native intermediate (NI). While a detailed description of the geometric and electronic structure of NI has been developed, this has been more elusive for PI largely due to the diamagnetic nature of its ground state. Density functional theory (DFT) calculations have been used to correlate to spectroscopic data to generate a description of the geometric and electronic structure of PI. A highly conserved carboxylate residue near the T2 site is found to play a critical role in stabilizing the PI structure, which induces oxidation of the T2 and one T3 Cu center and strong superexchange stabilization via the peroxide bridge, allowing irreversible binding of O2 at the trinuclear Cu site. Correlation of PI to NI is achieved using a two-dimensional potential energy surface generated to describe the catalytic two-electron reduction of the peroxide O-O bond by the MCOs. It is found that the reaction is thermodynamically driven by the relative stability of NI and the involvement of the simultaneous two-electron-transfer process. A low activation barrier (calculated approximately 5-6 kcal/mol and experimental approximately 3-5 kcal/mol) is produced by the triangular topology of the trinuclear Cu cluster site, as this symmetry provides good donor-acceptor frontier molecular orbital (FMO) overlap. Finally, the O-O bond cleavage in the trinuclear Cu cluster can be achieved via either a proton-assisted or a proton-unassisted process, allowing the MCOs to function over a wide range of pH. It is found that while the proton helps to stabilize the acceptor O22- sigma* orbital in the proton-assisted process for better donor-acceptor FMO overlap, the third oxidized Cu center in the trinuclear site assumes the role as a Lewis acid in the proton-unassisted process for similarly efficient O-O bond cleavage.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17918839-10551829,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17918839-10694398,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17918839-182231,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/17918839-9614947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17918839-9722559
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0002-7863
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
129
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13127-36
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pubmed:dateRevised |
2011-5-4
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pubmed:meshHeading |
pubmed-meshheading:17918839-Ceruloplasmin,
pubmed-meshheading:17918839-Computer Simulation,
pubmed-meshheading:17918839-Electrons,
pubmed-meshheading:17918839-Models, Molecular,
pubmed-meshheading:17918839-Oxidation-Reduction,
pubmed-meshheading:17918839-Oxygen,
pubmed-meshheading:17918839-Peroxides,
pubmed-meshheading:17918839-Protein Structure, Tertiary,
pubmed-meshheading:17918839-Protons
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pubmed:year |
2007
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pubmed:articleTitle |
Electronic structure of the peroxy intermediate and its correlation to the native intermediate in the multicopper oxidases: insights into the reductive cleavage of the o-o bond.
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pubmed:affiliation |
Department of Chemistry, Stanford University, Stanford, California 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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