In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 14, No. 12_Supplement_2 ( 2015-12-01), p. B44-B44
Abstract:
Protein tyrosine phosphatases play important roles in the signalling system in our bodies and were observed to be overexpressed in many diseases. For instance, PTP1B, the most famous member of this family, has a well-established role in diabetes mellitus, obesity and cancer. However, no PTP inhibitors have reached the market so far. This raised a question about the druggability of their catalytic site; which appears to be hydrophilic in nature and is believed to favour mainly polar ligands to bind with. In this study, we did an extensive data minding in the protein data bank to obtain all available crystal structures of all members in the PTP family. We analysed these crystal structures using SiteMap/Schrodinger. This software finds cavities in the examined proteins structure and evaluates these pockets according to their suitability for binding with drug-like ligands. Consequently, we classified PTPs according to their druggability scores; a representative of each category is shown and discussed accordingly. The influence of active site flexibility (open or closed) on PTPs druggability was studied. The effect of tight-bound water molecules on active site druggability was also assessed. This analysis can prove useful in the discovery of new PTP inhibitors and can help researchers to save unnecessary cost, money and efforts by prioritizing PTP targets according to which members have the most druggable catalytic pocket. Citation Format: Mohammad A. Ghattas, Noor Raslan, Asil Sadeq, Noor Atatreh. Druggability assessment of protein tyrosine phosphatase binding site. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B44.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-15-B44
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2062135-8
SSG:
12
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