PMID- 20831859
OWN - NLM
STAT- MEDLINE
DCOM- 20110228
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1807
IP  - 1
DP  - 2011 Jan
TI  - The identity of the transient proton loading site of the proton-pumping mechanism 
      of cytochrome c oxidase.
PG  - 80-4
LID - 10.1016/j.bbabio.2010.08.014 [doi]
AB  - Cellular respiration is driven by cytochrome c oxidase (CcO), which reduces 
      oxygen to water and couples the released energy to proton pumping across the 
      mitochondrial or bacterial membrane. Proton pumping in CcO involves proton 
      transfer from the negatively charged side of the membrane to a transient 
      proton-loading or pump site (PLS), before it is ejected to the opposite side. 
      Although many details of the reaction mechanism are known, the exact location of 
      the PLS has remained elusive. We report here results from combined classical 
      molecular dynamics simulations and continuum electrostatic calculations, which 
      show that the hydrogen-bonded system around the A-propionate of heme a(3) 
      dissociates reversibly upon reduction of heme a. The dissociation increases the 
      pK(a) value of the propionate to a value above ~9, making it accessible for 
      redox-state dependent protonation. The redox state of heme a is of key importance 
      in controlling proton leaks by polarizing the PLS both statically and 
      dynamically. These findings suggest that the propionate region of heme a(3) 
      fulfills the criteria of the pump site in the proton translocation mechanism of 
      CcO.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Kaila, Ville R I
AU  - Kaila VR
AD  - Helsinki Bioenergetics Group, Programme of Structural Biology and Biophysics, 
      Institute of Biotechnology, University of Helsinki, P.O. Box 65, FI-00014 
      Helsinki, Finland.
FAU - Sharma, Vivek
AU  - Sharma V
FAU - Wikstrom, Marten
AU  - Wikstrom M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100908
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Bacterial Proteins)
RN  - 0 (Proton Pumps)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 3.6.3.14 (Proton-Translocating ATPases)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/chemistry/metabolism
MH  - Binding Sites
MH  - Cattle
MH  - Electron Transport Complex IV/chemistry/*metabolism
MH  - Energy Transfer
MH  - Models, Molecular
MH  - Oxidation-Reduction
MH  - Probability
MH  - Protein Conformation
MH  - Proton Pumps/chemistry/*metabolism
MH  - Proton-Translocating ATPases/chemistry/metabolism
MH  - Static Electricity
EDAT- 2010/09/14 06:00
MHDA- 2011/03/01 06:00
CRDT- 2010/09/14 06:00
PHST- 2010/06/29 00:00 [received]
PHST- 2010/08/26 00:00 [revised]
PHST- 2010/08/31 00:00 [accepted]
PHST- 2010/09/14 06:00 [entrez]
PHST- 2010/09/14 06:00 [pubmed]
PHST- 2011/03/01 06:00 [medline]
AID - S0005-2728(10)00699-7 [pii]
AID - 10.1016/j.bbabio.2010.08.014 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2011 Jan;1807(1):80-4. doi: 10.1016/j.bbabio.2010.08.014. 
      Epub 2010 Sep 8.