http://scholars.ntou.edu.tw/handle/123456789/3579
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Shan-Meng Lin | en_US |
dc.contributor.author | Shih-Chao Lin | en_US |
dc.contributor.author | Jia-Ning Hsu | en_US |
dc.contributor.author | Chung-ke Chang | en_US |
dc.contributor.author | Ching-Ming Chien | en_US |
dc.contributor.author | Yong-Sheng Wang | en_US |
dc.contributor.author | Hung-Yi Wu | en_US |
dc.contributor.author | U-Ser Jeng | en_US |
dc.contributor.author | Kylene Kehn-Hall | en_US |
dc.contributor.author | Ming-Hon Hou | en_US |
dc.date.accessioned | 2020-11-18T08:15:33Z | - |
dc.date.available | 2020-11-18T08:15:33Z | - |
dc.date.issued | 2020-03 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://scholars.ntou.edu.tw/handle/123456789/3579 | - |
dc.description.abstract | Structure-based stabilization of protein–protein interactions (PPIs) is a promising strategy for drug discovery. However, this approach has mainly focused on the stabilization of native PPIs, and non-native PPIs have received little consideration. Here, we identified a non-native interaction interface on the three-dimensional dimeric structure of the N-terminal domain of the MERS-CoV nucleocapsid protein (MERS-CoV N-NTD). The interface formed a conserved hydrophobic cavity suitable for targeted drug screening. By considering the hydrophobic complementarity during the virtual screening step, we identified 5-benzyloxygramine as a new N protein PPI orthosteric stabilizer that exhibits both antiviral and N-NTD protein-stabilizing activities. X-ray crystallography and small-angle X-ray scattering showed that 5-benzyloxygramine stabilizes the N-NTD dimers through simultaneous hydrophobic interactions with both partners, resulting in abnormal N protein oligomerization that was further confirmed in the cell. This unique approach based on the identification and stabilization of non-native PPIs of N protein could be applied toward drug discovery against CoV diseases. | en_US |
dc.language.iso | en | en_US |
dc.publisher | American Chemical Society | en_US |
dc.relation.ispartof | Journal of Medicinal Chemistry | en_US |
dc.title | Structure-Based Stabilization of Non-native Protein-Protein Interactions of Coronavirus Nucleocapsid Proteins in Antiviral Drug Design | en_US |
dc.type | journal article | en_US |
dc.identifier.doi | 10.1021/acs.jmedchem.9b01913 | - |
dc.identifier.isi | 000526404600025 | - |
dc.relation.journalvolume | 63 | en_US |
dc.relation.journalissue | 6 | en_US |
dc.relation.pages | 3131–3141 | en_US |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.fulltext | no fulltext | - |
item.languageiso639-1 | en | - |
crisitem.author.dept | College of Life Sciences | - |
crisitem.author.dept | Bachelor Degree Program in Marine Biotechnology | - |
crisitem.author.dept | National Taiwan Ocean University,NTOU | - |
crisitem.author.orcid | 0000-0003-2942-5937 | - |
crisitem.author.parentorg | National Taiwan Ocean University,NTOU | - |
crisitem.author.parentorg | College of Life Sciences | - |
顯示於: | 海洋生物科技學士學位學程(系) |
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