Targeting allosteric sites for protein tyrosine phosphatase inhibition
- Authors
- 류성언; 김승준
- Issue Date
- Sep-2014
- Publisher
- 한국구조생물학회
- Citation
- Biodesign, v.2, no.3, pp.81 - 90
- Indexed
- KCI
OTHER
- Journal Title
- Biodesign
- Volume
- 2
- Number
- 3
- Start Page
- 81
- End Page
- 90
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/159151
- ISSN
- 2288-6982
- Abstract
- Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of phosphorylated protein substrates during cellsignaling processes. Although various PTPs have been implicated as drug targets for human diseases, there have beenno examples of therapeutics that target PTPs. Conventionally, PTP inhibitor developments mainly targeted the activesite pocket whose structural characteristics limited the discovery of optimal compounds with potency, selectivity andmembrane permeability. Recent approaches for allosteric inhibition have shed light on the development of therapeuticsthat 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 regionsgenerated by the opening of the flexible D-loop were identified as allosteric inhibition sites. In PTP1B, the C-terminaldisordered regions were found to bind novel non-competitive inhibitors. The novel inhibitors targeting those allosteric sitesshowed remarkable target-selectivity, potency, and in vivo activity. Approaches for allosteric inhibition provide excitingopportunities for the development of new PTP-targeting therapeutics for the effective treatment of cancer, diabetes,immune disorders and central nervous system diseases.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 공과대학 > 서울 생명공학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/159151)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.