Molecular Docking Identifies the Binding Sites of the Ligands Specifically to TCPTP

• 1、School of Pharmacy, Tianjin Medical University, TianJin 300070
• 2、School of Pharmacy, Tianjin Medical University,Tianjin 300070, China

Abstract：We have studied on T-cell protein-tyrosine phosphatase (TCPTP) as a model phosphatase in an attempt to seek the most favorable binding sites of TCPTP interacting with ligands and find out differences in substrate recognition by protein tyrosine phosphatase 1B (PTP1B) and TCPTP. The xalylarylaminobenzoic acids derivatives and 1,2,3,4-Tetrahydroisoquino- linyl (TIQ) sulfamic acid derivative were selected in this study. To better understand the structural and chemical features responsible for the recognition mechanism, the Autodock 4.0 was performed as automated molecular docking program to explore the binding pocket sites of this enzyme. Two key sites (Ⅰand Ⅲ) were found of the TCPTP contributing towards the binding of these compounds. SiteⅠ residues involved in forming two important hydrogen bonds from the enzyme were: Gln260 and Arg222. We also found that site Ⅲ consists of two main residues: Tyr22 and Pro262, which involved in hydrophobic interactions with the ligands. And the results of molecular docking showed that residue Asp48 played an important role in substrate binding. The interaction model of TCPTP inhibitors was similar and the difference in biologic activities of these inhibitors can be well explained. This study will help in the rational design of potent and selective PTP1B inhibitors over TCPTP.

keywords： TCPTP PTP1B molecular docking binding site

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