PMID- 37461851
OWN - NLM
STAT- MEDLINE
DCOM- 20231023
LR  - 20231023
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 25
IP  - 37
DP  - 2023 Sep 27
TI  - New insights into the proton pumping mechanism of ba(3) cytochrome c oxidase: the 
      functions of key residues and water.
PG  - 25105-25115
LID - 10.1039/d3cp01334k [doi]
AB  - As the terminal oxidase of cell respiration in mitochondria and aerobic bacteria, 
      the proton pumping mechanism of ba(3)-type cytochrome c oxidase (CcO) of Thermus 
      thermophiles is still not fully understood. Especially, the functions of key 
      residues which were considered as the possible proton loading sites (PLSs) above 
      the catalytic center, as well as water located above and within the catalytic 
      center, remain unclear. In this work, molecular dynamic simulations were 
      performed on a set of designed mutants of key residues (Asp287, Asp372, His376, 
      and Glu126(II)). The results showed that Asp287 may not be a PLS, but it could 
      modulate the ability of the proton transfer pathway to transfer protons through 
      its salt bridge with Arg225. Maintaining the closed state of the water pool above 
      the catalytic center is necessary for the participation of inside water molecules 
      in proton transfer. Water molecules inside the water pool can form hydrogen bond 
      chains with PLS to facilitate proton transfer. Additional quantum cluster models 
      of the Fe-Cu metal catalytic center are established, indicating that when the 
      proton is transferred from Tyr237, it is more likely to reach the O(Cu) atom 
      directly through only one water molecule. This work provides a more profound 
      understanding of the functions of important residues and specific water molecules 
      in the proton pumping mechanism of CcO.
FAU - Yang, Xiaoyue
AU  - Yang X
AD  - School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation 
      Technologies, Zhengzhou University, Henan 450001, China. yanglh@zzu.edu.cn.
FAU - Liu, Shaohui
AU  - Liu S
AD  - School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation 
      Technologies, Zhengzhou University, Henan 450001, China. yanglh@zzu.edu.cn.
FAU - Yin, Zhili
AU  - Yin Z
AD  - School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation 
      Technologies, Zhengzhou University, Henan 450001, China. yanglh@zzu.edu.cn.
FAU - Chen, Mengguo
AU  - Chen M
AD  - School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation 
      Technologies, Zhengzhou University, Henan 450001, China. yanglh@zzu.edu.cn.
FAU - Song, Jinshuai
AU  - Song J
AUID- ORCID: 0000-0002-1909-9253
AD  - Green Catalysis Center, and College of Chemistry, Zhengzhou University, Henan 
      450001, China.
FAU - Li, Pengfei
AU  - Li P
AUID- ORCID: 0000-0002-2572-5935
AD  - Department of Chemistry and Biochemistry, Loyola University Chicago, Illinois 
      60660, USA.
FAU - Yang, Longhua
AU  - Yang L
AUID- ORCID: 0000-0002-3583-8255
AD  - School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation 
      Technologies, Zhengzhou University, Henan 450001, China. yanglh@zzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230927
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - 0 (Proton Pumps)
RN  - 0 (Protons)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - *Electron Transport Complex IV/chemistry
MH  - *Proton Pumps
MH  - Protons
MH  - Water/chemistry
MH  - Molecular Dynamics Simulation
MH  - Oxidation-Reduction
EDAT- 2023/07/18 06:42
MHDA- 2023/10/23 00:42
CRDT- 2023/07/18 04:03
PHST- 2023/10/23 00:42 [medline]
PHST- 2023/07/18 06:42 [pubmed]
PHST- 2023/07/18 04:03 [entrez]
AID - 10.1039/d3cp01334k [doi]
PST - epublish
SO  - Phys Chem Chem Phys. 2023 Sep 27;25(37):25105-25115. doi: 10.1039/d3cp01334k.