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.
Highlights
Chicoric acid (CA; Figure 1A), a derivative of both caffeic acid and tartaric acid, known as cichoric acid and dicaffeoyltartaric acid, is the main phenolic compound found in Echinacea purpurea [1]
The inhibitory properties of CA against HIV-1 integrase were confirmed by computational modeling performed by one of the co-authors of the present paper [14]
In the present paper, using both computational modeling and experimental assays we have demonstrated that chicoric acid can bind to two binding sites in the YopH phosphatase enzyme and that the catalytic site is preferred
Summary
Chicoric acid (CA; Figure 1A), a derivative of both caffeic acid and tartaric acid, known as cichoric acid and dicaffeoyltartaric acid, is the main phenolic compound found in Echinacea purpurea [1]. It was identified in many plant families, including those of seagrass, horsetail, fern and lemon balm [2]. Chicoric acid is one of the numerous active ingredients (alkamides, polysaccharides, and glycoproteins) associated with human health benefits from E. purpurea dietary supplements [6, 7] and compared with other phenolic acids, it succeeds on the nutraceutical market. There are many studies on implications of other PTPs in cancer development [22, 23, 24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
