Oncotarget

Research Papers: Immunology:

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

Alicja Kuban-Jankowska _, Kamlesh K. Sahu, Magdalena Gorska, Jack A. Tuszynski and Michal Wozniak

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Oncotarget. 2016; 7:2229-2238. https://doi.org/10.18632/oncotarget.6812

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Abstract

Alicja Kuban-Jankowska1, Kamlesh K. Sahu2, Magdalena Gorska1, Jack A. Tuszynski2,3 and Michal Wozniak1

1 Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland

2 Department of Physics, University of Alberta, Edmonton, Canada

3 Division of Experimental Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada

Correspondence to:

Alicja Kuban-Jankowska, email:

Keywords: chicoric acid, caffeic acid, chlorogenic acid, protein tyrosine phosphatase YopH, Immunology and Microbiology Section, Immune response, Immunity

Received: September 10, 2015 Accepted: November 26, 2015 Published: January 01, 2016

Abstract

Chicoric acid (CA) is a phenolic compound present in dietary supplements with a large spectrum of biological properties reported ranging from antioxidant, to antiviral, to immunostimulatory properties. Due to the fact that chicoric acid promotes phagocytic activity and was reported as an allosteric inhibitor of the PTP1B phosphatase, we examined the effect of CA on YopH phosphatase from pathogenic bacteria, which block phagocytic processes of a host cell. We performed computational studies of chicoric acid binding to YopH as well as validation experiments with recombinant enzymes. In addition, we performed similar studies for caffeic and chlorogenic acids to compare the results. Docking experiments demonstrated that, from the tested compounds, only CA binds to both catalytic and secondary binding sites of YopH. Our experimental results showed that CA reduces activity of recombinant YopH phosphatase from Yersinia enterocolitica and human CD45 phosphatase. The inhibition caused by CA was irreversible and did not induce oxidation of catalytic cysteine. We proposed that inactivation of YopH induced by CA is involved with allosteric inhibition by interacting with essential regions responsible for ligand binding.


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