PMID- 18509049
OWN - NLM
STAT- MEDLINE
DCOM- 20080624
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 22
DP  - 2008 Jun 3
TI  - Electrostatic basis for the unidirectionality of the primary proton transfer in 
      cytochrome c oxidase.
PG  - 7726-31
LID - 10.1073/pnas.0800580105 [doi]
AB  - Gaining detailed understanding of the energetics of the proton-pumping process in 
      cytochrome c oxidase (CcO) is one of the challenges of modern biophysics. Despite 
      promising mechanistic proposals, most works have not related the activation 
      barriers of the different assumed steps to the protein structure, and there has 
      not been a physically consistent model that reproduced the barriers needed to 
      create a working pump. This work reevaluates the activation barriers for the 
      primary proton transfer (PT) steps by calculations that reflect all relevant free 
      energy contributions, including the electrostatic energies of the generated 
      charges, the energies of water insertion, and large structural rearrangements of 
      the donor and acceptor. The calculations have reproduced barriers that account 
      for the directionality and sequence of events in the primary PT in CcO. It has 
      also been found that the PT from Glu-286 (E) to the propionate of heme a(3) (Prd) 
      provides a gate for an initial back leakage from the high pH side of the 
      membrane. Interestingly, the rotation of E that brings it closer to Prd appears 
      to provide a way for blocking competing pathways in the primary PT. Our study 
      elucidates and quantifies the nature of the control of the directionality in the 
      primary PT in CcO and provides instructive insight into the role of the water 
      molecules in biological PT, showing that "bridges" of several water molecules in 
      hydrophobic regions present a problem (rather than a solution) that is minimized 
      in the primary PT.
FAU - Pisliakov, Andrei V
AU  - Pisliakov AV
AD  - Department of Chemistry, University of Southern California, 418 SGM Building, 
      3620 McClintock Avenue, Los Angeles, CA 90089-1062, USA. andrei@usc.edu
FAU - Sharma, Pankaz K
AU  - Sharma PK
FAU - Chu, Zhen T
AU  - Chu ZT
FAU - Haranczyk, Maciej
AU  - Haranczyk M
FAU - Warshel, Arieh
AU  - Warshel A
LA  - eng
GR  - R01 GM040283/GM/NIGMS NIH HHS/United States
GR  - R01 GM40283/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080528
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Protons)
RN  - 059QF0KO0R (Water)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Electron Transport Complex IV/*chemistry
MH  - Entropy
MH  - Protein Conformation
MH  - *Protons
MH  - Static Electricity
MH  - Water/*chemistry
PMC - PMC2409407
COIS- The authors declare no conflict of interest.
EDAT- 2008/05/30 09:00
MHDA- 2008/06/25 09:00
PMCR- 2008/12/03
CRDT- 2008/05/30 09:00
PHST- 2008/05/30 09:00 [pubmed]
PHST- 2008/06/25 09:00 [medline]
PHST- 2008/05/30 09:00 [entrez]
PHST- 2008/12/03 00:00 [pmc-release]
AID - 0800580105 [pii]
AID - 0184 [pii]
AID - 10.1073/pnas.0800580105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7726-31. doi: 
      10.1073/pnas.0800580105. Epub 2008 May 28.