PMID- 27605664
OWN - NLM
STAT- MEDLINE
DCOM- 20170524
LR  - 20210209
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 291
IP  - 46
DP  - 2016 Nov 11
TI  - The Mg2+-containing Water Cluster of Mammalian Cytochrome c Oxidase Collects Four 
      Pumping Proton Equivalents in Each Catalytic Cycle.
PG  - 23882-23894
AB  - Bovine heart cytochrome c oxidase (CcO) pumps four proton equivalents per 
      catalytic cycle through the H-pathway, a proton-conducting pathway, which 
      includes a hydrogen bond network and a water channel operating in tandem. Protons 
      are transferred by H(3)O(+) through the water channel from the N-side into the 
      hydrogen bond network, where they are pumped to the P-side by electrostatic 
      repulsion between protons and net positive charges created at heme a as a result 
      of electron donation to O(2) bound to heme a(3) To block backward proton 
      movement, the water channel remains closed after O(2) binding until the 
      sequential four-proton pumping process is complete. Thus, the hydrogen bond 
      network must collect four proton equivalents before O(2) binding. However, a 
      region with the capacity to accept four proton equivalents was not discernable in 
      the x-ray structures of the hydrogen bond network. The present x-ray structures 
      of oxidized/reduced bovine CcO are improved from 1.8/1.9 to 1.5/1.6 A resolution, 
      increasing the structural information by 1.7/1.6 times and revealing that a large 
      water cluster, which includes a Mg(2+) ion, is linked to the H-pathway. The 
      cluster contains enough proton acceptor groups to retain four proton equivalents. 
      The redox-coupled x-ray structural changes in Glu(198), which bridges the Mg(2+) 
      and Cu(A) (the initial electron acceptor from cytochrome c) sites, suggest that 
      the Cu(A)-Glu(198)-Mg(2+) system drives redox-coupled transfer of protons pooled 
      in the water cluster to the H-pathway. Thus, these x-ray structures indicate that 
      the Mg(2+)-containing water cluster is the crucial structural element providing 
      the effective proton pumping in bovine CcO.
CI  - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Yano, Naomine
AU  - Yano N
AD  - From the Picobiology Institute and.
FAU - Muramoto, Kazumasa
AU  - Muramoto K
AD  - the Department of Life Science, Graduate School of Life Science, University of 
      Hyogo, 3-2-1 Koto, Kamigori, Akoh, Hyogo 678-1297.
FAU - Shimada, Atsuhiro
AU  - Shimada A
AD  - From the Picobiology Institute and.
FAU - Takemura, Shuhei
AU  - Takemura S
AD  - From the Picobiology Institute and.
FAU - Baba, Junpei
AU  - Baba J
AD  - From the Picobiology Institute and.
FAU - Fujisawa, Hidenori
AU  - Fujisawa H
AD  - From the Picobiology Institute and.
FAU - Mochizuki, Masao
AU  - Mochizuki M
AD  - From the Picobiology Institute and.
FAU - Shinzawa-Itoh, Kyoko
AU  - Shinzawa-Itoh K
AD  - From the Picobiology Institute and.
FAU - Yamashita, Eiki
AU  - Yamashita E
AD  - the Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 
      565-0871, and.
FAU - Tsukihara, Tomitake
AU  - Tsukihara T
AD  - From the Picobiology Institute and.
AD  - the Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 
      565-0871, and.
AD  - JSJT, CREST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
FAU - Yoshikawa, Shinya
AU  - Yoshikawa S
AD  - From the Picobiology Institute and yoshi@sci.u-hyogo.ac.jp.
LA  - eng
SI  - PDB/2DYR
PT  - Journal Article
DEP - 20160907
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Proton Pumps)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - I38ZP9992A (Magnesium)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Crystallography, X-Ray
MH  - Electron Transport Complex IV/*chemistry/metabolism
MH  - Magnesium/*chemistry/metabolism
MH  - *Models, Molecular
MH  - Protein Structure, Quaternary
MH  - Proton Pumps/*chemistry/metabolism
MH  - Structure-Activity Relationship
PMC - PMC5104913
OTO - NOTNLM
OT  - bioenergetics
OT  - copper
OT  - cytochrome c oxidase (Complex IV)
OT  - heme
OT  - membrane protein
OT  - mitochondrial membrane potential
OT  - proton pump
OT  - x-ray crystallography
EDAT- 2016/09/09 06:00
MHDA- 2017/05/26 06:00
PMCR- 2017/11/11
CRDT- 2016/09/09 06:00
PHST- 2015/12/22 00:00 [received]
PHST- 2016/08/26 00:00 [revised]
PHST- 2016/09/09 06:00 [pubmed]
PHST- 2017/05/26 06:00 [medline]
PHST- 2016/09/09 06:00 [entrez]
PHST- 2017/11/11 00:00 [pmc-release]
AID - S0021-9258(20)34657-3 [pii]
AID - M115.711770 [pii]
AID - 10.1074/jbc.M115.711770 [doi]
PST - ppublish
SO  - J Biol Chem. 2016 Nov 11;291(46):23882-23894. doi: 10.1074/jbc.M115.711770. Epub 
      2016 Sep 7.