title: Chicoric acid binds to two sites and decreases the activity of the YopH bacterial virulence factor.
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.
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Kuban-Jankowska
authors.affiliation: Department of Physics, University of Alberta, Edmonton, Canada.
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Sahu
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gorska
authors.affiliation: Department of Physics, University of Alberta, Edmonton, Canada.|Division of Experimental Oncology, Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Canada.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Tuszynski
authors.affiliation: Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Wozniak
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002109:Caffeic Acids / Q000737:chemistry*; D020134:Catalytic Domain / Q000187:drug effects*; D002726:Chlorogenic Acid / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013386:Succinates / Q000737:chemistry*; D037521:Virulence Factors; D015008:Yersinia enterocolitica / Q000201:enzymology* / Q000472:pathogenicity
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002109:Caffeic Acids; D013386:Succinates; D037521:Virulence Factors; D002726:Chlorogenic Acid; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D003545:Cysteine; C100435:chicoric acid; C040048:caffeic acid
keywords: Immune response; Immunity; Immunology and Microbiology Section; caffeic acid; chicoric acid; chlorogenic acid; protein tyrosine phosphatase YopH