PMID- 25896562
OWN - NLM
STAT- MEDLINE
DCOM- 20150818
LR  - 20161126
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1847
IP  - 8
DP  - 2015 Aug
TI  - Role of subunit III and its lipids in the molecular mechanism of cytochrome c 
      oxidase.
PG  - 690-7
LID - S0005-2728(15)00065-1 [pii]
LID - 10.1016/j.bbabio.2015.04.007 [doi]
AB  - The terminal respiratory enzyme cytochrome c oxidase (CcO) reduces molecular 
      oxygen to water, and pumps protons across the inner mitochondrial membrane, or 
      the plasma membrane of bacteria. A two-subunit CcO harbors all the elements 
      necessary for oxygen reduction and proton pumping. However, it rapidly undergoes 
      turnover-induced irreversible damage, which is effectively prevented by the 
      presence of subunit III and its tightly bound lipids. We have performed classical 
      atomistic molecular dynamics (MD) simulations on a three-subunit CcO, which show 
      the formation of water wires between the polar head groups of lipid molecules 
      bound to subunit III and the proton uptake site Asp91 (Bos taurus enzyme 
      numbering). Continuum electrostatic calculations suggest that these lipids 
      directly influence the proton affinity of Asp91 by 1-2pK units. We surmise that 
      lipids bound to subunit III influence the rate of proton uptake through the 
      D-pathway, and therefore play a key role in preventing turnover-induced 
      inactivation. Atomistic MD simulations show that subunit III is rapidly hydrated 
      in the absence of internally bound lipids, which is likely to affect the rate of 
      O2 diffusion into the active-site. The role of subunit III with its indigenous 
      lipids in the molecular mechanism of CcO is discussed.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Sharma, Vivek
AU  - Sharma V
AD  - Department of Physics, Tampere University of Technology, FI-33101 Tampere, 
      Finland. Electronic address: vivek.sharma@tut.fi.
FAU - Ala-Vannesluoma, Pauliina
AU  - Ala-Vannesluoma P
AD  - Department of Physics, Tampere University of Technology, FI-33101 Tampere, 
      Finland.
FAU - Vattulainen, Ilpo
AU  - Vattulainen I
AD  - Department of Physics, Tampere University of Technology, FI-33101 Tampere, 
      Finland; MEMPHYS, Center for Biomembrane Physics, Department of Physics, 
      University of Southern Denmark, Odense, Denmark.
FAU - Wikstrom, Marten
AU  - Wikstrom M
AD  - Helsinki Bioenergetics Group, Programme for Structural Biology and Biophysics, 
      Institute of Biotechnology, University of Helsinki, FI-00014 Helsinki, Finland.
FAU - Rog, Tomasz
AU  - Rog T
AD  - Department of Physics, Tampere University of Technology, FI-33101 Tampere, 
      Finland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150417
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Lipids)
RN  - 0 (Protein Subunits)
RN  - 0 (Proton Pumps)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Binding Sites
MH  - Catalysis
MH  - Electron Transport Complex IV/*chemistry/*metabolism
MH  - Hydrogen-Ion Concentration
MH  - Lipids/*chemistry
MH  - Models, Molecular
MH  - Molecular Dynamics Simulation
MH  - Oxidation-Reduction
MH  - Oxygen/*metabolism
MH  - Protein Subunits
MH  - *Proton Pumps
MH  - Rhodobacter sphaeroides/enzymology
OTO - NOTNLM
OT  - Cardiolipin
OT  - Continuum electrostatic
OT  - Molecular dynamics simulation
OT  - Oxygen diffusion
OT  - Water molecule
EDAT- 2015/04/22 06:00
MHDA- 2015/08/19 06:00
CRDT- 2015/04/22 06:00
PHST- 2015/02/02 00:00 [received]
PHST- 2015/04/07 00:00 [revised]
PHST- 2015/04/12 00:00 [accepted]
PHST- 2015/04/22 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
AID - S0005-2728(15)00065-1 [pii]
AID - 10.1016/j.bbabio.2015.04.007 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2015 Aug;1847(8):690-7. doi: 10.1016/j.bbabio.2015.04.007. 
      Epub 2015 Apr 17.