PMID- 18430799
OWN - NLM
STAT- MEDLINE
DCOM- 20080522
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 105
IP  - 17
DP  - 2008 Apr 29
TI  - Glutamic acid 242 is a valve in the proton pump of cytochrome c oxidase.
PG  - 6255-9
LID - 10.1073/pnas.0800770105 [doi]
AB  - Aerobic life is based on a molecular machinery that utilizes oxygen as a terminal 
      electron sink. The membrane-bound cytochrome c oxidase (CcO) catalyzes the 
      reduction of oxygen to water in mitochondria and many bacteria. The energy 
      released in this reaction is conserved by pumping protons across the 
      mitochondrial or bacterial membrane, creating an electrochemical proton gradient 
      that drives production of ATP. A crucial question is how the protons pumped by 
      CcO are prevented from flowing backwards during the process. Here, we show by 
      molecular dynamics simulations that the conserved glutamic acid 242 near the 
      active site of CcO undergoes a protonation state-dependent conformational change, 
      which provides a valve in the pumping mechanism. The valve ensures that at any 
      point in time, the proton pathway across the membrane is effectively 
      discontinuous, thereby preventing thermodynamically favorable proton back-leakage 
      while maintaining an overall high efficiency of proton translocation. Suppression 
      of proton leakage is particularly important in mitochondria under physiological 
      conditions, where production of ATP takes place in the presence of a high 
      electrochemical proton gradient.
FAU - Kaila, Ville R I
AU  - Kaila VR
AD  - Helsinki Bioenergetics Group, Structural Biology and Biophysics Program, 
      Institute of Biotechnology, University of Helsinki, Viikinkaari 1, P.O. Box 65, 
      00014, Helsinki, Finland.
FAU - Verkhovsky, Michael I
AU  - Verkhovsky MI
FAU - Hummer, Gerhard
AU  - Hummer G
FAU - Wikstrom, Marten
AU  - Wikstrom M
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080422
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 (Proton Pumps)
RN  - 0 (Protons)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Electron Transport Complex IV/*chemistry/metabolism
MH  - Glutamic Acid/*chemistry
MH  - Isomerism
MH  - Models, Molecular
MH  - Proton Pumps/*chemistry
MH  - Protons
MH  - Thermodynamics
PMC - PMC2359812
COIS- The authors declare no conflict of interest.
EDAT- 2008/04/24 09:00
MHDA- 2008/05/23 09:00
PMCR- 2008/10/29
CRDT- 2008/04/24 09:00
PHST- 2008/04/24 09:00 [pubmed]
PHST- 2008/05/23 09:00 [medline]
PHST- 2008/04/24 09:00 [entrez]
PHST- 2008/10/29 00:00 [pmc-release]
AID - 0800770105 [pii]
AID - 0040 [pii]
AID - 10.1073/pnas.0800770105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6255-9. doi: 
      10.1073/pnas.0800770105. Epub 2008 Apr 22.