PMID- 25418102
OWN - NLM
STAT- MEDLINE
DCOM- 20150723
LR  - 20181113
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 107
IP  - 9
DP  - 2014 Nov 4
TI  - Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from 
      Thermus thermophilus.
PG  - 2177-84
LID - S0006-3495(14)00948-5 [pii]
LID - 10.1016/j.bpj.2014.09.010 [doi]
AB  - A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes 
      the reduction of molecular oxygen to water in the mitochondrial and bacterial 
      membranes. Substrate electrons and protons are taken up from different sides of 
      the membrane and protons are pumped across the membrane, thereby generating an 
      electrochemical gradient. The well-studied A-type CcO uses two different entry 
      channels for protons: the D-channel for all pumped and two consumed protons, and 
      the K-channel for the other two consumed protons. In contrast, the B-type CcO 
      uses only a single proton input channel for all consumed and pumped protons. It 
      has the same location as the A-type K-channel (and thus is named the K-channel 
      analog) without sharing any significant sequence homology. In this study, we 
      performed molecular-dynamics simulations and electrostatic calculations to 
      characterize the K-channel analog in terms of its energetic requirements and 
      functionalities. The function of Glu-15B as a proton sink at the channel entrance 
      is demonstrated by its rotational movement out of the channel when it is 
      deprotonated and by its high pKA value when it points inside the channel. Tyr-244 
      in the middle of the channel is identified as the valve that ensures 
      unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the 
      K-channel analog only while being deprotonated. The electrostatic energy 
      landscape was calculated for all proton-transfer steps in the K-channel analog, 
      which functions via proton-hole transfer. Overall, the K-channel analog has a 
      very stable geometry without large energy barriers.
FAU - Woelke, Anna Lena
AU  - Woelke AL
AD  - Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, 
      Germany.
FAU - Wagner, Anke
AU  - Wagner A
AD  - Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, 
      Germany.
FAU - Galstyan, Gegham
AU  - Galstyan G
AD  - Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, 
      Germany.
FAU - Meyer, Tim
AU  - Meyer T
AD  - Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, 
      Germany.
FAU - Knapp, Ernst-Walter
AU  - Knapp EW
AD  - Institute of Chemistry and Biochemistry, Freie Universitat Berlin, Berlin, 
      Germany. Electronic address: knapp@chemie.fu-berlin.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (Bacterial Proteins)
RN  - 0 (Proton Pumps)
RN  - 0 (Protons)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Bacterial Proteins/*chemistry/genetics
MH  - Electron Transport Complex IV/*chemistry/genetics
MH  - Hydrogen Bonding
MH  - Molecular Dynamics Simulation
MH  - Proton Pumps/*chemistry
MH  - *Protons
MH  - Rotation
MH  - Static Electricity
MH  - Thermus thermophilus
PMC - PMC4223178
EDAT- 2014/11/25 06:00
MHDA- 2015/07/24 06:00
PMCR- 2015/11/04
CRDT- 2014/11/25 06:00
PHST- 2014/06/30 00:00 [received]
PHST- 2014/09/03 00:00 [revised]
PHST- 2014/09/11 00:00 [accepted]
PHST- 2014/11/25 06:00 [entrez]
PHST- 2014/11/25 06:00 [pubmed]
PHST- 2015/07/24 06:00 [medline]
PHST- 2015/11/04 00:00 [pmc-release]
AID - S0006-3495(14)00948-5 [pii]
AID - 10.1016/j.bpj.2014.09.010 [doi]
PST - ppublish
SO  - Biophys J. 2014 Nov 4;107(9):2177-84. doi: 10.1016/j.bpj.2014.09.010.