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Title 

High-resolution crystal structure of the catalytic domain of human dual-specificity phosphatase 26

Authors 

Eun Young WonY XieC TakemotoL ChenZ J LiuB C WangD LeeEui-jeon WooSung Goo ParkM ShirouzuS YokoyamaSeung Jun KimSeung-Wook Chi

Publisher 

International Union of Crystallography

Issue Date 

2013

Citation 

Acta Crystallographica. Section D, Biological Crystallography, vol. 69, no. 6, pp. 1160-1170

Keywords 

catalytic domaindomain swappingDUSP26PTP

Abstract 

Dual-specificity phosphatases (DUSPs) play an important role in regulating cellular signalling pathways governing cell growth, differentiation and apoptosis. Human DUSP26 inhibits the apoptosis of cancer cells by dephosphorylating substrates such as p38 and p53. High-resolution crystal structures of the DUSP26 catalytic domain (DUSP26-C) and its C152S mutant [DUSP26-C (C152S)] have been determined at 1.67 and 2.20 14; ? resolution, respectively. The structure of DUSP26-C showed a novel type of domain-swapped dimer formed by extensive crossover of the C-terminal α7 helix. Taken together with the results of a phosphatase-activity assay, structural comparison with other DUSPs revealed that DUSP26-C adopts a catalytically inactive conformation of the protein tyrosine phosphate-binding loop which significantly deviates from that of canonical DUSP structures. In particular, a noticeable difference exists between DUSP26-C and the active forms of other DUSPs at the hinge region of a swapped C-terminal domain. Additionally, two significant gaps were identified between the catalytic core and its surrounding loops in DUSP26-C, which can be exploited as additional binding sites for allosteric enzyme regulation. The high-resolution structure of DUSP26-C may thus provide structural insights into the rational design of DUSP26-targeted anticancer drugs.

Citation 

Acta Crystallographica. Section D, Biological Crystallography, 69(6): 1160-1170

ISSN 

0907-4449

Link 

http://dx.doi.org/10.1107/S0907444913004770

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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