Inactivation of Phosphoserine/Threonine Phosphatase PstP in H37Rv Mycobacterium tuberculosis by In silico Drug Design Approach

Introduction: Mycobacterium tuberculosis (Mtb) is the aetiological agent of the infectious disease tuberculosis (TB). According to the World Health Organization’s most recent study, kinases play a crucial role in phosphorylation by transferring phosphate moieties to target proteins, while phosphatases reverse this process by dephosphorylating substrates or regulating kinase activity, restoring proteins to their unphosphorylated state.Method: Several software, programs and databases were used to predict and calculate the interaction between target protein and ligand molecules.Results: Protein phosphatases are essential components in cellular signalling pathways mediated by phosphorylation. Despite the presenceof eleven serine/threonine protein kinases in Mtb, only one of them, namely phosphoserine/threonine phosphatase (PstP), has been identified. PstP stands out as a promising drug target due to its singular role as the exclusive phosphatase in Mtb. Serine/threonine protein phosphatase (PDB ID: 2cm1) was docked using AutoDock Vina software with ligands collected from other studies conducted on Mycobacterium tuberculosis. Virtual screening was carried out using ZincPharmer to find the homologous molecules to load the pharmacophore.Conclusion: Mycobacterium tuberculosis H37Rv has multiple targets for new drug design procedures. This is due to the variation in the proteins. PstP protein has five pockets and was given a good docking score with eight safe inhibitors for further studies, and eight tested molecules with PubChem_IDs 50956528, 7388777, 46780845, 3635532, 46954451, 1494562, 540267, 79107978, which have good features and can bind to PstP protein. How to cite this article:Abdul Jalil A A, Yaseen O Q, Khalaf S N. Inactivation of Phosphoserine/Threonine Phosphatase PstP in H37Rv Mycobacterium tuberculosis by In silico Drug Design Approach. J Commun Dis. 2024;56(3):74-80. DOI: https://doi.org/10.24321/0019.5138.202452