A hinge of the endogeneous ATP synthase inhibitor protein: The link between inhibitory and anchoring domains

2006 ◽  
Vol 65 (4) ◽  
pp. 999-1007 ◽  
Author(s):  
L. Domínguez-Ramírez ◽  
A. Gómez-Puyou ◽  
M. Tuena de Gómez-Puyou
Keyword(s):  
Atp Synthase ◽  
Inhibitor Protein ◽  
Synthase Inhibitor

Stoichiometry and Topology of the Complex of the Endogenous ATP Synthase Inhibitor Protein IF1with Calmodulin

Biochemistry ◽  
2010 ◽  
Vol 49 (35) ◽  
pp. 7542-7552 ◽  
Author(s):  
Daniela Pagnozzi ◽  
Leila Birolo ◽  
Gabriella Leo ◽  
Stefania Contessi ◽  
Giovanna Lippe ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Inhibitor Protein ◽  
And Topology ◽  
Synthase Inhibitor

scholarly journals The ATP synthase inhibitor protein IF1 plays a significant role in cancer metabolic flexibility

2018 ◽  
Vol 1859 ◽  
pp. e33
Author(s):  
Alessandra Baracca ◽  
Gianluca Sgarbi ◽  
Simona Barbato ◽  
Giulia Gorini ◽  
Francesca Liuzzi ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Significant Role ◽  
Metabolic Flexibility ◽  
Inhibitor Protein ◽  
Synthase Inhibitor

scholarly journals On the role of the ATP synthase inhibitor protein, IF 1 , in tumor bioenergetics

2016 ◽  
Vol 1857 ◽  
pp. e109
Author(s):  
Simona Barbato ◽  
Giulia Gorini ◽  
Gianluca Sgarbi ◽  
Anna Costanzini ◽  
Giancarlo Solaini ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Inhibitor Protein ◽  
Synthase Inhibitor ◽  
Tumor Bioenergetics

scholarly journals Genome-Wide Screening Identifies Six Genes That Are Associated with Susceptibility to Escherichia coli Microcin PDI

2015 ◽  
Vol 81 (20) ◽  
pp. 6953-6963 ◽  
Author(s):  
Zhe Zhao ◽  
Lauren J. Eberhart ◽  
Lisa H. Orfe ◽  
Shao-Yeh Lu ◽  
Thomas E. Besser ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Atp Synthase ◽  
Disulfide Bonds ◽  
Gene Knockout ◽  
Single Gene ◽  
Site Directed Mutagenesis ◽  
Content Type ◽  
E Coli ◽  
Synthase Inhibitor ◽  
Loss Of Susceptibility

ABSTRACTThe microcin PDI inhibits a diverse group of pathogenicEscherichia colistrains. Coculture of a single-gene knockout library (BW25113;n= 3,985 mutants) against a microcin PDI-producing strain (E. coli25) identified six mutants that were not susceptible (ΔatpA, ΔatpF, ΔdsbA, ΔdsbB, ΔompF, and ΔompR). Complementation of these genes restored susceptibility in all cases, and the loss of susceptibility was confirmed through independent gene knockouts inE. coliO157:H7 Sakai. Heterologous expression ofE. coliompFconferred susceptibility toSalmonella entericaandYersinia enterocoliticastrains that are normally unaffected by microcin PDI. The expression of chimeric OmpF and site-directed mutagenesis revealed that the K47G48N49region within the first extracellular loop ofE. coliOmpF is a putative binding site for microcin PDI. OmpR is a transcriptional regulator forompF, and consequently loss of susceptibility by the ΔompRstrain most likely is related to this function. Deletion of AtpA and AtpF, as well as AtpE and AtpH (missed in the original library screen), resulted in the loss of susceptibility to microcin PDI and the loss of ATP synthase function. Coculture of a susceptible strain in the presence of an ATP synthase inhibitor resulted in a loss of susceptibility, confirming that a functional ATP synthase complex is required for microcin PDI activity. Intransexpression ofompFin the ΔdsbAand ΔdsbBstrains did not restore a susceptible phenotype, indicating that these proteins are probably involved with the formation of disulfide bonds for OmpF or microcin PDI.

scholarly journals TBAJ-876 Displays Bedaquiline-Like Mycobactericidal Potency without Retaining the Parental Drug’s Uncoupler Activity

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Jickky Palmae Sarathy ◽  
Priya Ragunathan ◽  
Christopher B. Cooper ◽  
Anna M. Upton ◽  
Gerhard Grüber ◽  
...  
Keyword(s):  
Electron Transport ◽  
Atp Synthase ◽  
Mechanism Of Action ◽  
Bactericidal Activity ◽  
Atp Synthesis ◽  
Synthase Inhibitor ◽  
Time Kill

ABSTRACT The diarylquinoline F1FO-ATP synthase inhibitor bedaquiline (BDQ) displays protonophore activity. Thus, uncoupling electron transport from ATP synthesis appears to be a second mechanism of action of this antimycobacterial drug. Here, we show that the new BDQ analogue TBAJ-876 did not retain the parental drug’s protonophore activity. Comparative time-kill analyses revealed that both compounds exert the same bactericidal activity. These results suggest that the uncoupler activity is not required for the bactericidal activity of diarylquinolines.

scholarly journals Temporal Phosphoproteome Dynamics Induced by an ATP Synthase Inhibitor Citreoviridin

2015 ◽  
Vol 14 (12) ◽  
pp. 3284-3298 ◽  
Author(s):  
Chia-Wei Hu ◽  
Chia-Lang Hsu ◽  
Yu-Chao Wang ◽  
Yasushi Ishihama ◽  
Wei-Chi Ku ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Synthase Inhibitor

scholarly journals Energy Conservation by the H2:Heterodisulfide Oxidoreductase from Methanosarcina mazei Gö1: Identification of Two Proton-Translocating Segments

1999 ◽  
Vol 181 (13) ◽  
pp. 4076-4080 ◽  
Author(s):  
Tina Ide ◽  
Sebastian Bäumer ◽  
Uwe Deppenmeier
Keyword(s):  
Electron Transport ◽  
Atp Synthase ◽  
Cytoplasmic Membrane ◽  
Respiratory Control ◽  
Atp Synthesis ◽  
Heterodisulfide Reductase ◽  
Methanosarcina Mazei ◽  
Energy Conserving ◽  
Membrane Bound ◽  
Synthase Inhibitor

ABSTRACT The membrane-bound H2:heterodisulfide oxidoreductase system of the methanogenic archaeon Methanosarcina mazeiGö1 catalyzed the H2-dependent reduction of 2-hydroxyphenazine and the dihydro-2-hydroxyphenazine-dependent reduction of the heterodisulfide of HS-CoM and HS-CoB (CoM-S-S-CoB). Washed inverted vesicles of this organism were found to couple both processes with the transfer of protons across the cytoplasmic membrane. The maximal H+/2e− ratio was 0.9 for each reaction. The electrochemical proton gradient (ΔμH+ ) thereby generated was shown to drive ATP synthesis from ADP plus Pi, exhibiting stoichiometries of 0.25 ATP synthesized per two electrons transported for both partial reactions. ATP synthesis and the generation of ΔμH+ were abolished by the uncoupler 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847). The ATP synthase inhibitorN,N′-dicyclohexylcarbodiimide did not affect H+ translocation but led to an almost complete inhibition of ATP synthesis and decreased the electron transport rates. The latter effect was relieved by the addition of SF 6847. Thus, the energy-conserving systems showed a stringent coupling which resembles the phenomenon of respiratory control. The results indicate that two different proton-translocating segments are present in the H2:heterodisulfide oxidoreductase system; the first involves the 2-hydroxyphenazine-dependent hydrogenase, and the second involves the heterodisulfide reductase.

scholarly journals ATP Synthase Inhibition of Mycobacterium avium Is Not Bactericidal

2009 ◽  
Vol 53 (11) ◽  
pp. 4927-4929 ◽  
Author(s):  
Nacer Lounis ◽  
Tom Gevers ◽  
Joke Van Den Berg ◽  
Luc Vranckx ◽  
Koen Andries
Keyword(s):  
Atp Synthase ◽  
Mycobacterium Avium ◽  
Minimal Bactericidal Concentration ◽  
Bacteriostatic Effect ◽  
Synthase Inhibitor ◽  
Very High

ABSTRACT The efficacy of ATP synthase inhibitor TMC207 was assessed in early and late Mycobacterium avium infections in mice. In contrast to what was earlier observed for M. tuberculosis, a bacteriostatic effect was obtained. In vitro, the minimal bactericidal concentration (MBC)/MIC ratio was very high. The MBC was more relevant for assessment of pharmacokinetic/pharmacodynamic relationships than the MIC.

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