PMID- 17350588
OWN - NLM
STAT- MEDLINE
DCOM- 20070504
LR  - 20240312
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1767
IP  - 3
DP  - 2007 Mar
TI  - Exploring pathways and barriers for coupled ET/PT in cytochrome c oxidase: a 
      general framework for examining energetics and mechanistic alternatives.
PG  - 244-60
AB  - Gaining a detailed understanding of the energetics of the proton pumping process 
      in cytochrome c oxidase (CcO) is one of the challenges of modern biophysics. 
      Although there are several current mechanistic proposals, most of these ideas 
      have not been subjected to consistent structure-function considerations. In 
      particular most works have not related the activation barriers for different 
      mechanistic proposals to the protein structure. The present work describes a 
      general approach for exploring the energetics of different feasible models of the 
      action of CcO, using the observed protein structure, established simulation 
      methods and a modified Marcus' formulation. We start by reviewing our methods for 
      evaluation of the energy diagrams for different proton translocation paths and 
      then present a systematic analysis of various constraints that should be imposed 
      on any energy diagram for the pumping process. After the general analysis we turn 
      to the actual computational study, where we construct energy diagrams for forward 
      and backward paths, using the estimated calculated reduction potentials and pK(a) 
      values of all the relevant sites (including internal water molecules). We then 
      explore the relationship between the calculated energy diagrams and key 
      experimental constraints. This comparison allows us to identify some barriers 
      that are not fully consistent with the overall requirement for an efficient 
      pumping. In particular we identify back leakage channels, which are hard to block 
      without stopping the forward channels. This helps to identify open problems that 
      will require further experimental and theoretical studies. We also consider 
      reasonable adjustments of the calculated barriers that may lead to a working 
      pump. Although the present analysis does not establish a unique and workable 
      model for the mechanism of CcO, it presents what is probably the most consistent 
      current analysis of the barriers for different feasible pathways. Perhaps more 
      importantly, the framework developed here should provide a general way for 
      examining any proposal for the action of CcO as well as for the analysis of 
      further experimental findings about the action of this fascinating system.
FAU - Olsson, Mats H M
AU  - Olsson MH
AD  - University of Southern California, 3620 McClintock Avenue, Department of 
      Chemistry, SGM 418, Los Angeles, CA 90089-1062, USA. molsson@usc.edu
FAU - Siegbahn, Per E M
AU  - Siegbahn PE
FAU - Blomberg, Margareta R A
AU  - Blomberg MR
FAU - Warshel, Arieh
AU  - Warshel A
LA  - eng
GR  - R01 GM024492/GM/NIGMS NIH HHS/United States
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
PT  - Research Support, Non-U.S. Gov't
DEP - 20070130
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Proton Pumps)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Computer Simulation
MH  - Electron Transport
MH  - Electron Transport Complex IV/*chemistry/*metabolism
MH  - *Models, Biological
MH  - *Models, Molecular
MH  - Proton Pumps/*chemistry
MH  - Static Electricity
PMC - PMC2025695
MID - NIHMS20460
EDAT- 2007/03/14 09:00
MHDA- 2007/05/05 09:00
PMCR- 2008/03/01
CRDT- 2007/03/14 09:00
PHST- 2006/12/06 00:00 [received]
PHST- 2007/01/19 00:00 [revised]
PHST- 2007/01/24 00:00 [accepted]
PHST- 2007/03/14 09:00 [pubmed]
PHST- 2007/05/05 09:00 [medline]
PHST- 2007/03/14 09:00 [entrez]
PHST- 2008/03/01 00:00 [pmc-release]
AID - S0005-2728(07)00019-9 [pii]
AID - 10.1016/j.bbabio.2007.01.015 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2007 Mar;1767(3):244-60. doi: 10.1016/j.bbabio.2007.01.015. 
      Epub 2007 Jan 30.