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dc.contributor.authorHuang, Kuan-Weien_US
dc.contributor.authorHsu, Kai-Chengen_US
dc.contributor.authorChu, Lee-Yaen_US
dc.contributor.authorYang, Jinn-Moonen_US
dc.contributor.authorYuan, Hanna S.en_US
dc.contributor.authorHsiao, Yu-Yuanen_US
dc.date.accessioned2017-04-21T06:55:22Z-
dc.date.available2017-04-21T06:55:22Z-
dc.date.issued2016-09-08en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://dx.doi.org/10.1021/acs.jmedchem.6b00794en_US
dc.identifier.urihttp://hdl.handle.net/11536/134239-
dc.description.abstractThe DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human, DEDDh exonucleases can serve as antiviral drug targets due to their critical roles virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors for DEDDh exonucleases. We further show that two of the inhibitors, ATA and PV6R, indeed inhibit the exonuclease activity of the viral protein NP exonuclease of Lassa fever virus in vitro. Moreover, we determine the crystal structure of CRN-4 in complex with MES that reveals a unique inhibition Mechanism, by inducing the general base His179 to shift out of the active site. Our results not only provide the structural basis for the inhibition mechanism but also suggest potential lead inhibitors for the DEDDh exonucleases that may pave the way for designing nuclease inhibitors for biochemical and biomedical applications.en_US
dc.language.isoen_USen_US
dc.titleIdentification of Inhibitors for the DEDDh Family of Exonucleases and a Unique Inhibition Mechanism by Crystal Structure Analysis of CRN-4 Bound with 2-Morpholin-4-ylethanesulfonate (MES)en_US
dc.identifier.doi10.1021/acs.jmedchem.6b00794en_US
dc.identifier.journalJOURNAL OF MEDICINAL CHEMISTRYen_US
dc.citation.volume59en_US
dc.citation.issue17en_US
dc.citation.spage8019en_US
dc.citation.epage8029en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.department生物資訊及系統生物研究所zh_TW
dc.contributor.department分子醫學與生物工程研究所zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.contributor.departmentInstitute of Molecular Medicine and Bioengineeringen_US
dc.identifier.wosnumberWOS:000383111300022en_US
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