PMID- 33705281
OWN - NLM
STAT- MEDLINE
DCOM- 20210510
LR  - 20210510
IS  - 1608-3040 (Electronic)
IS  - 0006-2979 (Linking)
VI  - 86
IP  - 1
DP  - 2021 Jan
TI  - Mechanism of Inhibition of Cytochrome c Oxidase by Triton X-100.
PG  - 44-58
LID - 10.1134/S0006297921010053 [doi]
AB  - It is known that Triton X-100 (TX) reversibly inhibits activity of cytochrome c 
      oxidase (CcO). The mechanism of inhibition is analyzed in this work. The action 
      of TX is not directed to the reaction of CcO with cytochrome c, does not cause 
      transition of the enzyme to the "slow" form, and is not associated with 
      monomerization of the enzyme complex. TX completely suppresses oxygen reduction 
      by CcO, but inhibition is prevented and partially reversed by 
      dodecyl-beta-D-maltoside (DDM), a detergent used to maintain CcO in solution. A 1/1 
      stoichiometry competition is shown between DDM and TX for binding to CcO, with 
      K(i) = 0.3 mM and affinity of DDM for the enzyme of 1.2 mM. TX interaction with 
      the oxidized enzyme induces spectral response with maximum at 421 nm and 
      [TX](1/2) = 0.28 mM, presumably associated with heme a(3). When CcO interacts 
      with excess of H2O2 TX affects equilibrium of the oxygen intermediates of the 
      catalytic center accelerating the F(I)-607 --> F(II)-580 transition, inhibits 
      generation of O(2)(.-) by the enzyme, and, to a lesser extent, suppresses the 
      catalase partial activity. The observed effects can be explained by inhibition of 
      the conversion of the intermediate F(II)-580 to the free oxidized state during 
      the catalytic cycle. TX suppresses intraprotein electron transfer between hemes a 
      and a(3) during enzyme turnover. Partial peroxidase activity of CcO remains 
      relatively resistant to TX under conditions that block oxidase reaction 
      effectively. These features indicate an impairment of the K proton channel 
      conductivity. We suggest that TX interacts with CcO at the Bile Acid Binding Site 
      (BABS) that is located on the subunit I at the K-channel mouth and contacts with 
      amphipathic regulators of CcO [Buhrow et al. (2013) Biochemistry, 52, 6995-7006]. 
      Apparently, TX mimics the physiological ligand of BABS, whereas the DDM molecule 
      mimics an endogenous phospholipid bound at the edge of BABS that controls 
      effective affinity for the ligand.
FAU - Oleynikov, Ilya P
AU  - Oleynikov IP
AD  - Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 
      Moscow, 119992, Russia.
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, 119992, Russia.
FAU - Azarkina, Natalia V
AU  - Azarkina NV
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, 119992, Russia. azarkina@yahoo.com.
FAU - Vygodina, Tatiana V
AU  - Vygodina TV
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, 119992, Russia.
FAU - Konstantinov, Alexander A
AU  - Konstantinov AA
AD  - Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State 
      University, Moscow, 119992, Russia.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biochemistry (Mosc)
JT  - Biochemistry. Biokhimiia
JID - 0376536
RN  - 0 (Ligands)
RN  - 9002-93-1 (Octoxynol)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Electron Transport
MH  - Electron Transport Complex IV/*antagonists & inhibitors/metabolism
MH  - Kinetics
MH  - Ligands
MH  - Mitochondria, Heart/enzymology
MH  - Octoxynol/*pharmacology
OTO - NOTNLM
OT  - K-cnannel
OT  - Triton X-100
OT  - amphipathic ligands
OT  - cytochrome c oxidase
OT  - regulation
EDAT- 2021/03/12 06:00
MHDA- 2021/05/11 06:00
CRDT- 2021/03/11 17:17
PHST- 2021/03/11 17:17 [entrez]
PHST- 2021/03/12 06:00 [pubmed]
PHST- 2021/05/11 06:00 [medline]
AID - BCM86010056 [pii]
AID - 10.1134/S0006297921010053 [doi]
PST - ppublish
SO  - Biochemistry (Mosc). 2021 Jan;86(1):44-58. doi: 10.1134/S0006297921010053.