Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/141772
Title: Structural analysis of protein tyrosine phosphatase 1B reveals potentially druggable allosteric binding sites
Authors: Kumar, Ammu Prasanna
Nguyen, Minh Nhan
Verma, Chandra
Lukman, Suryani
Keywords: Science::Biological sciences
Issue Date: 2018
Source: Kumar, A. P., Nguyen, M. N., Verma, C., & Lukman, S. (2018). Structural analysis of protein tyrosine phosphatase 1B reveals potentially druggable allosteric binding sites. Protein, 86(3), 301-321. doi:10.1002/prot.25440
Journal: Proteins: Structure, Function and Bioinformatics
Abstract: Catalytic proteins such as human protein tyrosine phosphatase 1B (PTP1B), with conserved and highly polar active sites, warrant the discovery of druggable nonactive sites, such as allosteric sites, and potentially, therapeutic small molecules that can bind to these sites. Catalyzing the dephosphorylation of numerous substrates, PTP1B is physiologically important in intracellular signal transduction pathways in diverse cell types and tissues. Aberrant PTP1B is associated with obesity, diabetes, cancers, and neurodegenerative disorders. Utilizing clustering methods (based on root mean square deviation, principal component analysis, nonnegative matrix factorization, and independent component analysis), we have examined multiple PTP1B structures. Using the resulting representative structures in different conformational states, we determined consensus clustroids and used them to identify both known and novel binding sites, some of which are potentially allosteric. We report several lead compounds that could potentially bind to the novel PTP1B binding sites and can be further optimized. Considering the possibility for drug repurposing, we discovered homologous binding sites in other proteins, with ligands that could potentially bind to the novel PTP1B binding sites.
URI: https://hdl.handle.net/10356/141772
ISSN: 0887-3585
DOI: 10.1002/prot.25440
Rights: © 2017 Wiley Periodicals, Inc. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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