Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions

• Published in: Journal of microbiology and biotechnology Vol. 27; no. 5; pp. 878 - 895
• Main Authors: R, Harikrishna Reddy, Kim, Hackyoung, Cha, Seungbin, Lee, Bongsoo, Kim, Young Jun
• Format: Journal Article
• Language: English
• Published: Korea (South) 한국미생물·생명공학회 28.05.2017
• Subjects: Catalytic Domain; Diabetes Mellitus - drug therapy; Disease; Drug Delivery Systems; Drug Design; Drug Discovery; Drug Evaluation, Preclinical; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; Models, Molecular; Molecular Docking Simulation; Neoplasms - drug therapy; Phosphoric Monoester Hydrolases - physiology; Phosphorylation - physiology; Phosphotransferases - physiology; Protein Conformation; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - drug effects; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - physiology; Protein Tyrosine Phosphatases - chemistry; Protein Tyrosine Phosphatases - classification; Protein Tyrosine Phosphatases - drug effects; Protein Tyrosine Phosphatases - physiology; 생물학; Allosteric targeting; cancers; molecular docking; drug designing; diabetes; protein tyrosine phosphatases
• ISSN: 1017-7825; 1738-8872
• DOI: 10.4014/jmb.1701.01079

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.