Inactivation of Protein Tyrosine Phosphatases by Peracids Correlates with the Hydrocarbon Chain Length

Kuban–Jankowska, Alicja; Górska, M.; Tuszyński, Jack A.; Churchill, Cassandra D. M.; Winter, Philip; Kłobukowski, Mariusz; Woźniak, Michał

doi:10.1159/000430280

Cited by 12 publications

(7 citation statements)

References 46 publications

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“…Many studies showed that the enzymatic activity of PTPs can be reduced by oxidation of the catalytic cysteine residue [ 43 , 44 , 46 ], which we have also previously demonstrated for peracids [ 47 ]. To study the mechanism of chicoric acid caused inactivation of YopH, we decided to examine the amount of non-oxidized thiols groups.…”

Section: Resultssupporting

confidence: 68%

Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor

et al. 2016

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Section: Resultssupporting

confidence: 68%

Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor

et al. 2016

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“…Our previous results confirmed that, in comparison to hydrogen peroxide, selected carboxylic acids, e.g. octanoic acid, possess a significantly higher binding affinity for PTPs active sites and can be strong inhibitors of PTPs, including PTP1B [13].…”

Section: Introductionsupporting

confidence: 80%

Docosahexaenoic Acid Inhibits PTP1B Phosphatase and the Viability of MCF-7 Breast Cancer Cells

et al. 2019

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Background: Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid compound present in deep water fishes and dietary supplements, with a wide spectrum of potential health benefits, ranging from neurological to anti-inflammatory. Methods: Due to the fact that DHA is considered a breast cancer risk reducer, we examined the impact of DHA on MCF-7 breast cancer cells’ viability and its inhibitory properties on protein tyrosine phosphatase 1B (PTP1B), a pro-oncogenic phosphatase. Results: We found that DHA is able to lower both the enzymatic activity of PTP1B phosphatase and the viability of MCF-7 breast cancer cells. We showed that unsaturated DHA possesses a significantly higher inhibitory activity toward PTP1B in comparison to similar fatty acids. We also performed a computational analysis of DHA binding to PTP1B and discovered that it is able to bind to an allosteric binding site. Conclusions: Utilizing both a recombinant enzyme and cellular models, we demonstrated that DHA can be considered a potential pharmacological agent for the prevention of breast cancer.

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“…YopH recombinant phosphatase from Yersinia pestis and Yersinia eneterocolitica was treated with ATA and IC 50 values were calculated. We also treated YopHs with peroctanoic acid, containing a peroxycarboxyl group with a higher oxidizing potency than that of a carboxyl group, studied by our group as a strong PTP inhibitor [ 20 ], in order to compare the inhibitory effects. In addition, the human CD45 recombinant protein tyrosine phosphatase was utilized to study the inhibitory properties of ATA on human PTP.…”

Section: Resultsmentioning

confidence: 99%

Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor ofYersinia pestis

et al. 2015

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YopH is a bacterial protein tyrosine phosphatase, which is essential for the viability and pathogenic virulence of the plague-causing Yersinia sp. bacteria. Inactivation of YopH activity would lead to the loss of bacterial pathogenicity. We have studied the inhibitory properties of aurintricarboxylic acid (ATA) against YopH phosphatase and found that at nanomolar concentrations ATA reversibly decreases the activity of YopH. Computational docking studies indicated that in all binding poses ATA binds in the YopH active site. Molecular dynamics simulations showed that in the predicted binding pose, ATA binds to the essential Cys403 and Arg409 residues in the active site and has a stronger binding affinity than the natural substrate (pTyr). The cyclic voltammetry experiments suggest that ATA reacts remarkably strongly with molecular oxygen. Additionally, the electrochemical reduction of ATA in the presence of a negative potential from −2.0 to 2.5 V generates a current signal, which is observed for hydrogen peroxide. Here we showed that ATA indicates a unique mechanism of YopH inactivation due to a redox process. We proposed that the potent inhibitory properties of ATA are a result of its strong binding in the YopH active site and in situ generation of hydrogen peroxide near catalytic cysteine residue.

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Inactivation of Protein Tyrosine Phosphatases by Peracids Correlates with the Hydrocarbon Chain Length

Cited by 12 publications

References 46 publications

Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor

Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor

Docosahexaenoic Acid Inhibits PTP1B Phosphatase and the Viability of MCF-7 Breast Cancer Cells

Redox process is crucial for inhibitory properties of aurintricarboxylic acid against activity of YopH: virulence factor ofYersinia pestis

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