An Integrated Computational Hierarchy for Identification of Potent Inhibitors Against Shikimate Kinase Enzyme from Shigella Sonnei, a Major Cause of Global Dysentery

Shikimate Kinase is an enzyme of shikimate pathway, characterized as non-paralog, non-homolog, and essential for bacterial survival. Shikimate Kinase enzyme assists in catalysis of the ATP-dependent phosphorylation of shikimate to produce shikimate 3-phosphate. The absence of Shikimate Kinase in human makes the enzyme more attractive and fascinating target to search for potential inhibitor against the said enzyme. The objective of current study is the identification of potent inhibitors against Shikimate Kinase of S. sonnei. The model of Shikimate Kinase is generated using a comparative molecular modeling approach and the best model is selected based on stereochemical properties. Active site of Shikimate Kinase found conserved across twenty pathogenic species of bacteria. Docking scrutiny showed that compounds zinc_2135897 and CB4275815 have reliable binding interactions as they gained highest GOLD fitness scores and showed hydrogen bonding with Arg139 that is involved in the shikimate-carboxylate group recognition. These compounds revealed realistic Shikimate Kinase inhibitory activity and can be more active to design derivatives with modified actions.