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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. November 2003, Volume 2, Number 11, 732-740 |
Theoretical Study of Hydrogen-Bonded Network and Proton
Transfer in the Active Site of Reduced Cytochrome c Oxidase
Yasunori Yoshioka and Masaki Mitani
Internet Electron. J. Mol. Des. 2003, 2, 732-740
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Abstract:
There are many proposals of reaction mechanisms of
O2-reduction catalyzed by cytochrome c oxidase (CcO) and the
mechanism is not still conclusive. We have previously proposed
new 'water-proton transport' (WPT) mechanism in which H2O
hydrogen-bonded to His290 and Tyr244 transports a proton to
FeOO to yield FeOOH. The path through which a proton is
transferred to this H2O molecule in the active site of CcO is
investigated from theoretical viewpoint in this work. The
moderate size of model of the active site in CcO was constructed
based on the geometry of fully reduced form 1OCR in PDB. All
histidines were modeled by imidazoles and Tyr244 by phenol.
The key fragments concerned with the hydrogen-bonded network
were geometrically optimized. The hybrid exchange-correlation
functional B3LYP method was employed with double-zeta basis
set. The H2O molecule exists between farnesylethyl and Thr316
by hydrogen bonds and the hydrogen-bonded network, which is
connecting from Lys319 to the active site of O2-reduction, is
formed in the reduced CcO. The proton necessary for
O2-reduction is provided through this hydrogen-bonded network.
The proton is trapped on farnesylethyl of heme a3, subsequently
the proton is transferred to Tyr244 to give a proton to the H2O
molecule between His290 and Tyr244. The energy barrier of the
proton transfer is qualitatively estimated to be 12 kcal/mol. The
proton path, which is necessary to perform the O2-reduction, was
made clear from the theoretical viewpoint.
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