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The family-wide structure and function of human dual-specificity protein phosphatases

Title
The family-wide structure and function of human dual-specificity protein phosphatases
Author
김재관
Issue Date
2014-02
Publisher
WILEY-BLACKWELL
Citation
Acta Crystallographica Section D, 2014, 70(2), P.421-435
Abstract
Dual-specificity protein phosphatases (DUSPs), which dephosphorylate both phosphoserine/threonine and phosphotyrosine, play vital roles in immune activation, brain function and cell-growth signalling. A family-wide structural library of human DUSPs was constructed based on experimental structure determination supplemented with homology modelling. The catalytic domain of each individual DUSP has characteristic features in the active site and in surface-charge distribution, indicating substrate-interaction specificity. The active-site loop-to-strand switch occurs in a subtype-specific manner, indicating that the switch process is necessary for characteristic substrate interactions in the corresponding DUSPs. A comprehensive analysis of the activity inhibition profile and active-site geometry of DUSPs revealed a novel role of the active-pocket structure in the substrate specificity of DUSPs. A structure-based analysis of redox responses indicated that the additional cysteine residues are important for the protection of enzyme activity. The family-wide structures of DUSPs form a basis for the understanding of phosphorylation-mediated signal transduction and the development of therapeutics.
URI
https://scripts.iucr.org/cgi-bin/paper?mh5099
ISSN
0907-4449; 1399-0047
DOI
10.1107/S1399004713029866
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