Targeting allosteric sites for protein tyrosine phosphatase inhibition
- Title
- Targeting allosteric sites for protein tyrosine phosphatase inhibition
- Author
- 류성언
- Issue Date
- 2014-09
- Publisher
- 한국구조생물학회. / Korean Society for Structural Biology.
- Citation
- Biodesign 2.3 (2014): 81-90.
- Abstract
- Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of phosphorylated protein substrates during cell||||signaling processes. Although various PTPs have been implicated as drug targets for human diseases, there have been no examples of therapeutics that target PTPs. Conventionally, PTP inhibitor developments mainly targeted the active site pocket whose structural characteristics limited the discovery of optimal compounds with potency, selectivity and membrane permeability. Recent approaches for allosteric inhibition have shed light on the development of therapeutics that target PTPs, and three classes of allosteric sites were identified in different members of PTPs. In a receptor-type PTP (RPTP), CD45, a domain interface pocket was targeted for allosteric inhibition. In MKP-4 and DUSP6, the crevice regions generated by the opening of the flexible D-loop were identified as allosteric inhibition sites. In PTP1B, the C-terminal disordered regions were found to bind novel non-competitive inhibitors. The novel inhibitors targeting those allosteric sites showed remarkable target-selectivity, potency, and in vivo activity. Approaches for allosteric inhibition provide exciting opportunities for the development of new PTP-targeting therapeutics for the effective treatment of cancer, diabetes, immune disorders and central nervous system diseases.
- URI
- http://scholar.dkyobobook.co.kr/searchDetail.laf?barcode=4010025969620#http://hdl.handle.net/20.500.11754/52268
- ISSN
- 2288-6982; 2288-7105
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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