Kuban-Jankowska Alicja, Sahu Kamlesh K, Gorska Magdalena, Tuszynski Jack A, Wozniak Michal
Department of Medical Chemistry, Medical University of Gdansk, Gdansk, Poland.
Department of Physics, University of Alberta, Edmonton, Canada.
Oncotarget. 2016 Jan 19;7(3):2229-38. doi: 10.18632/oncotarget.6812.
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.
菊苣酸（CA）是一种存在于膳食补充剂中的酚类化合物，据报道具有广泛的生物学特性，从抗氧化到抗病毒，再到免疫刺激特性。由于菊苣酸能促进吞噬活性，并且被报道为蛋白酪氨酸磷酸酶1B（PTP1B）的变构抑制剂，我们研究了CA对病原菌YopH磷酸酶的影响，该酶会阻断宿主细胞的吞噬过程。我们进行了菊苣酸与YopH结合的计算研究以及重组酶的验证实验。此外，我们对咖啡酸和绿原酸进行了类似研究以比较结果。对接实验表明，在所测试的化合物中，只有CA能与YopH的催化位点和二级结合位点结合。我们的实验结果表明，CA可降低小肠结肠炎耶尔森菌重组YopH磷酸酶和人CD45磷酸酶的活性。CA引起的抑制作用是不可逆的，且不会诱导催化半胱氨酸的氧化。我们提出，CA诱导的YopH失活与通过与负责配体结合的关键区域相互作用的变构抑制有关。
