Crystal structure of unlinked NS2B-NS3 protease from Zika virus
Zika virus (ZIKV) has rapidly emerged as a global public health concern. Viral NS2B-NS3 protease processes viral polyprotein and is essential for the virus replication, making it an attractive antiviral drug target. We report crystal structures at 1.58-angstrom resolution of the unlinked NS2B-NS3 pr...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2017
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| Online Access: | https://hdl.handle.net/10356/84352 http://hdl.handle.net/10220/43576 |
| _version_ | 1826118377964306432 |
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| author | Zhang, Zhenzhen Li, Yan Loh, Ying Ru Phoo, Wint Wint Hung, Alvin W. Kang, CongBao Luo, Dahai |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Zhang, Zhenzhen Li, Yan Loh, Ying Ru Phoo, Wint Wint Hung, Alvin W. Kang, CongBao Luo, Dahai |
| author_sort | Zhang, Zhenzhen |
| collection | NTU |
| description | Zika virus (ZIKV) has rapidly emerged as a global public health concern. Viral NS2B-NS3 protease processes viral polyprotein and is essential for the virus replication, making it an attractive antiviral drug target. We report crystal structures at 1.58-angstrom resolution of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site. The unlinked NS2B-NS3 protease adopts a closed conformation in which NS2B engages NS3 to form an empty substrate-binding site. A second protease in the same crystal binds to the residues K14K15G16E17 from the neighboring NS3 in reverse orientation, resisting proteolysis. These features of ZIKV NS2B-NS3 protease may accelerate the discovery of structure-based antiviral drugs against ZIKV and related pathogenic flaviviruses. |
| first_indexed | 2024-10-01T04:42:24Z |
| format | Journal Article |
| id | ntu-10356/84352 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:42:24Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/843522020-11-01T05:18:54Z Crystal structure of unlinked NS2B-NS3 protease from Zika virus Zhang, Zhenzhen Li, Yan Loh, Ying Ru Phoo, Wint Wint Hung, Alvin W. Kang, CongBao Luo, Dahai Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Crystal Structure Zika Virus Zika virus (ZIKV) has rapidly emerged as a global public health concern. Viral NS2B-NS3 protease processes viral polyprotein and is essential for the virus replication, making it an attractive antiviral drug target. We report crystal structures at 1.58-angstrom resolution of the unlinked NS2B-NS3 protease from ZIKV as free enzyme and bound to a peptide reversely oriented at the active site. The unlinked NS2B-NS3 protease adopts a closed conformation in which NS2B engages NS3 to form an empty substrate-binding site. A second protease in the same crystal binds to the residues K14K15G16E17 from the neighboring NS3 in reverse orientation, resisting proteolysis. These features of ZIKV NS2B-NS3 protease may accelerate the discovery of structure-based antiviral drugs against ZIKV and related pathogenic flaviviruses. ASTAR (Agency for Sci., Tech. and Research, S’pore) Accepted version 2017-08-14T06:07:08Z 2019-12-06T15:43:22Z 2017-08-14T06:07:08Z 2019-12-06T15:43:22Z 2016 Journal Article Zhang, Z., Li, Y., Loh, Y. R., Phoo, W. W., Hung, A. W., Kang, C., et al. (2016). Crystal structure of unlinked NS2B-NS3 protease from Zika virus. Science, 354(6319), 1597-1600. 0036-8075 https://hdl.handle.net/10356/84352 http://hdl.handle.net/10220/43576 10.1126/science.aai9309 en Science © 2016 The Author(s). This is the author created version of a work that has been peer reviewed and accepted for publication in Science, published by American Association for the Advancement of Science on behalf of The Author(s). It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1126/science.aai9309]. 5 p. application/pdf |
| spellingShingle | Crystal Structure Zika Virus Zhang, Zhenzhen Li, Yan Loh, Ying Ru Phoo, Wint Wint Hung, Alvin W. Kang, CongBao Luo, Dahai Crystal structure of unlinked NS2B-NS3 protease from Zika virus |
| title | Crystal structure of unlinked NS2B-NS3 protease from Zika virus |
| title_full | Crystal structure of unlinked NS2B-NS3 protease from Zika virus |
| title_fullStr | Crystal structure of unlinked NS2B-NS3 protease from Zika virus |
| title_full_unstemmed | Crystal structure of unlinked NS2B-NS3 protease from Zika virus |
| title_short | Crystal structure of unlinked NS2B-NS3 protease from Zika virus |
| title_sort | crystal structure of unlinked ns2b ns3 protease from zika virus |
| topic | Crystal Structure Zika Virus |
| url | https://hdl.handle.net/10356/84352 http://hdl.handle.net/10220/43576 |
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