DC Field | Value | Language |
---|---|---|
dc.contributor.author | Eun Young Won | - |
dc.contributor.author | Sang-Ok Lee | - |
dc.contributor.author | Dong-Hwa Lee | - |
dc.contributor.author | D Lee | - |
dc.contributor.author | Kwang-Hee Bae | - |
dc.contributor.author | Sang Chul Lee | - |
dc.contributor.author | Seung Jun Kim | - |
dc.contributor.author | Seung-Wook Chi | - |
dc.date.accessioned | 2017-04-19T10:27:45Z | - |
dc.date.available | 2017-04-19T10:27:45Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | 10.1371/journal.pone.0162115 | ko |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/13449 | - |
dc.description.abstract | Human dual-specificity phosphatase 26 (DUSP26) is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61-211, DUSP26-C), the high-resolution structure of its catalytically active form has not been resolved. In this study, we determined the crystal structure of a catalytically active form of DUSP26 (residues 39-211, DUSP26-N) with an additional N-terminal region at 2.0 A resolution. Unlike the C-terminal domain-swapped dimeric structure of DUSP26-C, the DUSP26-N (C152S) monomer adopts a fold-back conformation of the C-terminal a8-helix and has an additional a1-helix in the N-terminal region. Consistent with the canonically active conformation of its protein tyrosine phosphate-binding loop (PTP loop) observed in the structure, the phosphatase assay results demonstrated that DUSP26-N has significantly higher catalytic activity than DUSP26-C. Furthermore, size exclusion chromatography-multiangle laser scattering (SEC-MALS) measurements showed that DUSP26-N (C152S) exists as a monomer in solution. Notably, the crystal structure of DUSP26-N (C152S) revealed that the N-terminal region of DUSP26-N (C152S) serves a scaffolding role by positioning the surrounding a7-a8 loop for interaction with the PTP-loop through formation of an extensive hydrogen bond network, which seems to be critical in making the PTP-loop conformation competent for phosphatase activity. Our study provides the first high-resolution structure of a catalytically active form of DUSP26, which will contribute to the structurebased rational design of novel DUSP26-targeting anticancer therapeutics. | - |
dc.publisher | Public Library of Science | - |
dc.title | Structural insight into the critical role of the N-terminal region in the catalytic activity of dual-specificity phosphatase 26 | - |
dc.title.alternative | Structural insight into the critical role of the N-terminal region in the catalytic activity of dual-specificity phosphatase 26 | - |
dc.type | Article | - |
dc.citation.title | PLoS One | - |
dc.citation.number | 9 | - |
dc.citation.endPage | e0162115 | - |
dc.citation.startPage | e0162115 | - |
dc.citation.volume | 11 | - |
dc.contributor.affiliatedAuthor | Eun Young Won | - |
dc.contributor.affiliatedAuthor | Sang-Ok Lee | - |
dc.contributor.affiliatedAuthor | Dong-Hwa Lee | - |
dc.contributor.affiliatedAuthor | Kwang-Hee Bae | - |
dc.contributor.affiliatedAuthor | Sang Chul Lee | - |
dc.contributor.affiliatedAuthor | Seung Jun Kim | - |
dc.contributor.affiliatedAuthor | Seung-Wook Chi | - |
dc.contributor.alternativeName | 원은영 | - |
dc.contributor.alternativeName | 이상옥 | - |
dc.contributor.alternativeName | 이동화 | - |
dc.contributor.alternativeName | 이대엽 | - |
dc.contributor.alternativeName | 배광희 | - |
dc.contributor.alternativeName | 이상철 | - |
dc.contributor.alternativeName | 김승준 | - |
dc.contributor.alternativeName | 지승욱 | - |
dc.identifier.bibliographicCitation | PLoS One, vol. 11, no. 9, pp. e0162115-e0162115 | - |
dc.identifier.doi | 10.1371/journal.pone.0162115 | - |
dc.description.journalClass | Y | - |
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