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

Kuban-Jankowska, Alicja; Sahu, Kamlesh K; Niedzialkowski, Pawel; Gorska, Magdalena; Tuszynski, Jack A; Ossowski, Tadeusz; Wozniak, Michal

To study the binding conformation of ATA in the YopH active site we performed molecular dynamics simulations using Amber12 and identified top scoring ATA in presence and absence of catalase (500U/ml). The enzymatic activity of YopH was measured on microplate reader as absorbance at 405 nm using pNPP substrate. Data presented as percent of control, means ± SD (n = 10). T-test analysis of variance. *significantly different (P < 0.001) from control, **significantly different (P < 0.001) in pairs. B. Activity of CD45 after treatment with 200 nM and 500 nM ATA in presence and absence of catalase. The enzymatic activity of CD45 was measured on microplate reader as absorbance at 405 nm using pNPP substrate. Data presented as percent of control, means ± SD (n = 10). T-test analysis of variance. * significantly different (P < 0.001) from control, **significantly different (P < 0.001) in pairs. poses from docking studies. The interactions of ATA in the YopH binding site are presented as a PLIF diagram (protein ligand interaction fingerprints) in Figure 6A . The dotted line around the molecule shows solvent contact and dotted arrows represent hydrogen bonds between amino acid residues from YopH and ATA. In the predicted binding pose two carboxyl groups of ATA are directed toward essential Cys403 and Arg409 residues in the YopH active site. Under such steric conditions there is likelihood of hydrogen bond formation between the arginine residue and carboxyl groups of ATA. As shown in the PLIF diagram, ATA has been able to utilize its polar groups to interact electrostatically with Cys403, Arg409 and water ( Figure 6A ). The positively charged arginine residue of the YopH active site is likely to attract the negatively charged carboxyl groups from ATA.