Crystal structure of O-Acetylserine sulfhydralase (OASS) isoform 3 from Entamoeba histolytica: Pharmacophore-based virtual screening and validation of novel inhibitors

Structure-based inhibitor screening of natural products against NSP15 of SARS-CoV-2 revealed thymopentin and oleuropein as potent inhibitors

“…Molecular dynamic simulation is considered to be a reliable approach with greater insight into the dynamic behavior of proteins and that of the ligand conformations as observed in our earlier studies (Dharavath et al 2020;Waziri et al 2019;Sharma et al 2018). The simulations provide detailed information to better understand the motions of the individual atoms as a function of time and properties of the molecules.…”

“…Molecular dynamics (MD) simulations were conducted for the modeled systems in an explicit solvent using the Groningen Machine for Chemical Simulations (GROMACS) package according to our previously described methodology (Vijayan et al 2016;Waziri et al 2019;Sharma et al 2018;Dharavath et al 2020). Molecular dynamics simulations were performed for the top five screened compounds (Thymopentin, Ginsenoside, Oleuropein, Akebia Saponin D, and Keampferitrin), using the GROMOS 53A6 force field (Berk and Erik 2008) to understand the dynamic behaviour, structural stability, residual fluctuation, and compactness of the protein in its complex form.…”

“…These docking algorithms are most commonly used to estimate the binding affinity and binding pose of the inhibitor and the enzyme. The identification of the inhibitors for various targets using these docking and virtual screening algorithms obtained high successful rate based on our previous studies (Vijayan et al 2016;Dharavath et al 2020;Waziri et al 2019). Therefore, we used all of the above-mentioned software to dock the Selleckchem Natural Product database (https:// www.…”

Inhibiting Pyridoxal Kinase of Entamoeba histolytica Is Lethal for This Pathogen

“…In particular, it may spread to the liver and brain to cause abscess and cerebral amoebiasis (Tanyuksel and Petri, 2003). Enzymes of the sulfur metabolism pathway such as O-acetylserine sulfhydrylase contain PLP as a cofactor and play an important role in the antioxidative defence mechanism (Raj et al, 2013;Jeelani and Nozaki, 2016) which has been targeted to develop inhibitors in E. histolytica (Nagpal et al, 2012;Ansari et al, 2016;Dharavath et al, 2020). Similarly, other PLP containing enzymes: aspartate aminotransferase, methionine gamma-lyase, cysteine desulfurylase, threonine dehydratase and phosphoserine amino transferase are equally important drug targets (Tokoro et al, 2003;Sato et al, 2008;Sato et al, 2017).…”

“…Similarly, other PLP containing enzymes: aspartate aminotransferase, methionine gamma-lyase, cysteine desulfurylase, threonine dehydratase and phosphoserine amino transferase are equally important drug targets (Tokoro et al, 2003;Sato et al, 2008;Sato et al, 2017). We have been extensively characterizing some of these enzymes as potential therapeutic targets for structure based drug discovery, (Kumar et al, 2011;Kumari et al, 2019;Singh et al, 2019;Dharavath et al, 2020) and what remained something of utmost importance was to target pyridoxal kinase itself, which catalyses the formation PLP in E. histolytica. In our previous work, we have biochemically characterized and determined the crystal structures of pyridoxal kinase from E. histolytica where a single copy of this gene exists for the synthesis of PLP through the salvage pathway (Tarique et al, 2020).…”