Identification of Mycobacterium tuberculosis CtpF as a target for designing new antituberculous compounds

Santos, Paola; López‐Vallejo, Fabian; Ramírez, David; Caballero, Julio; Espinosa, Dulce Mata; Hernández-Pando, Rogelio; Soto, Carlos Y.

doi:10.1016/j.bmc.2019.115256

Cited by 8 publications

(11 citation statements)

References 47 publications

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“…Modeled structure of CtpF using Ca 2+ -bound SERCA1a in E1 confirmation (PDB code 1SU4) as the template is shown in Figure S1. Model of CtpF in an alternate confirmation E2 (with inhibitor Cyclopiazonic Acid bound) was reported recently (Santos et al, 2020). Although our results, in general, are in broad agreement with theirs, there are a few subtle differences.…”

Section: Ctpf Is a Bonafide Calcium Atpasesupporting

confidence: 91%

“…Notably, the observation that CtpF is not essential in vitro but provides a survival advantage to the intracellular Mtb, reaffirms its potential as a drug target. The modeling studies presented by us and others (Santos et al, 2020) provide some insights in this direction. Similar to SERCA ATPase (Olesen et al, 2007;Di Marino et al, 2015), CtpF may also exist in a number of conformational states including the calcium bound and unbound forms.…”

Section: Discussionmentioning

confidence: 78%

“…Similar to SERCA ATPase (Olesen et al, 2007 ; Di Marino et al, 2015 ), CtpF may also exist in a number of conformational states including the calcium bound and unbound forms. The inhibitor of the ATPase, C PA appears to lock the protein in calcium free conformation similar to its action on SERCA (Santos et al, 2020 ). The binding sites for the drug and calcium are largely non-overlapping and the inhibition seen (Santos et al, 2020 ) is likely by allosteric mode and the drug binding would block the channel of calcium entry.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitor of the ATPase, C PA appears to lock the protein in calcium free conformation similar to its action on SERCA (Santos et al, 2020 ). The binding sites for the drug and calcium are largely non-overlapping and the inhibition seen (Santos et al, 2020 ) is likely by allosteric mode and the drug binding would block the channel of calcium entry. Thus, binding of the drug and calcium to the protein appears to be mutually exclusive.…”

Section: Discussionmentioning

confidence: 99%

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Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner

Garg

Borbora

Bansia

et al. 2020

Front. Cell. Infect. Microbiol.

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Calcium is a very important second messenger, whose concentration in various cellular compartments is under tight regulation. A disturbance in the levels of calcium in these compartments can play havoc in the cell, as it regulates various cellular processes by direct or indirect mechanisms. Here, we have investigated the functional importance of a calcium transporting P2A ATPase, CtpF of Mycobacterium tuberculosis (Mtb) in the pathogen's interaction with the host. Among its uncanny ways of dealing with the host with umpteen strategies for survival and persistence in humans, CtpF is identified as a new player. The levels of ctpF are upregulated in macrophage stresses like hypoxia, high nitric oxide levels and acidic pH. Using confocal microscopy and fluorimetry, we show that CtpF effluxes calcium in macrophages in early stages of Mtb infection. Downregulation of ctpF expression by conditional knockdown resulted in perturbation of host calcium levels and consequent decreased activation of mTOR. We present a mechanism how calcium efflux by the pathogen inhibits mTOR-dependent autophagy and enhances bacterial survival. Our work highlights how Mtb engages its metal efflux pumps to exploit host autophagic process for its proliferation.

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Section: Ctpf Is a Bonafide Calcium Atpasesupporting

confidence: 91%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner

Garg

Borbora

Bansia

et al. 2020

Front. Cell. Infect. Microbiol.

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“…CPA is an example of blocking signaling cascade in bacteria so that its extracellular transportation and tough bacterial infection could be inhibited. The recent literature had delivered essential findings about mycobacterial ctpF that include molecular docking and virtual screening that lead to the identification of effective inhibitor of the ATPase activity of the protein [44,45,46].…”

Section: Mycobacterial P-type Atpasesmentioning

confidence: 99%

Calcium ATPase signaling: A must include mechanism in the Radar of therapeutics development against Tuberculosis

Shivangi

Meena

2020

Biotechnology and Applied Biochemistry

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An article presented by Peterson and Verkhratsky in 2016 explores the linkage of calcium and adenosine triphosphate (ATP) for a themed issue of Evolution Brings Ca 2+ and ATP Together to Control Life and Death. The article impacted due to several findings of their cooperative functioning such as the formulation of ATP necessitates a small concentration of cytosolic Ca 2+ , and therefore leads these two molecules together. The low cytosolic Ca 2+ concentration is a primary advantage of its function like a universal secondary messenger. The present article also explores the essential facts about Ca 2+ -ATP signaling in response to tuberculosis (TB). TB is still a major causal mortality of an important fraction of worldwide population and therefore we require an urgent regimen for its treatment. The new strategies that cover all forms of the disease multidrug-resistant TB, extensively drug-resistant TB, and TDR are necessity to overcome the disease pattern and its outcomes. Ionophores and channels-mediated transportation of Ca 2+ that leads to the elevation of intracellular Ca 2+ concentration provides an important clue to divert the focus toward this signaling mechanism. P2X7 pathway is an enormous Ca 2+ signaling pathway that incorporated Ca 2+ influx and potassium efflux upon activation by ATP molecule. After this activation, immune components like 1L-12 and IL-6 release and generate a protective response against pathogen. This review highlights importance of togetherness of Ca 2+ and ATP signaling with new and more emphasized view of Ca 2+ regulation.

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P-Type ATPases: A Relevant Component in Mycobacterium tuberculosis Viability

et al. 2023

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Identification of Mycobacterium tuberculosis CtpF as a target for designing new antituberculous compounds

Cited by 8 publications

References 47 publications

Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner

Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner

Calcium ATPase signaling: A must include mechanism in the Radar of therapeutics development against Tuberculosis

P-Type ATPases: A Relevant Component in Mycobacterium tuberculosis Viability

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