Structure of the NS2B-NS3 protease from Zika virus after self-cleavage
The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2017
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| Online Access: | https://hdl.handle.net/10356/83027 http://hdl.handle.net/10220/42379 |
| _version_ | 1826111606299295744 |
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| author | Phoo, Wint Wint Li, Yan Zhang, Zhenzhen Lee, Michelle Yueqi Loh, Ying Ru Tan, Yaw Bia Ng, Elizabeth Yihui Lescar, Julien Kang, CongBao Luo, Dahai |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Phoo, Wint Wint Li, Yan Zhang, Zhenzhen Lee, Michelle Yueqi Loh, Ying Ru Tan, Yaw Bia Ng, Elizabeth Yihui Lescar, Julien Kang, CongBao Luo, Dahai |
| author_sort | Phoo, Wint Wint |
| collection | NTU |
| description | The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non-structural protein NS2B-NS3 protease with the last four amino acids of the NS2B cofactor bound at the NS3 active site. This structure represents a post-proteolysis state of the enzyme during viral polyprotein processing and provides insights into peptide substrate recognition by the protease. Nuclear magnetic resonance (NMR) studies and protease activity assays unravel the protein dynamics upon binding the protease inhibitor BPTI in solution and confirm this finding. The structural and functional insights of the ZIKV protease presented here should advance our current understanding of flavivirus replication and accelerate structure-based antiviral drug discovery against ZIKV. |
| first_indexed | 2024-10-01T02:53:30Z |
| format | Journal Article |
| id | ntu-10356/83027 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:53:30Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/830272020-11-01T05:12:21Z Structure of the NS2B-NS3 protease from Zika virus after self-cleavage Phoo, Wint Wint Li, Yan Zhang, Zhenzhen Lee, Michelle Yueqi Loh, Ying Ru Tan, Yaw Bia Ng, Elizabeth Yihui Lescar, Julien Kang, CongBao Luo, Dahai School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) NTU Institute of Structural Biology Zika virus NS2B-NS3 The recent outbreak of Zika virus (ZIKV) infections in the Americas represents a serious threat to the global public health. The viral protease that processes viral polyproteins during infection appears as an attractive drug target. Here we report a crystal structure at 1.84 Å resolution of ZIKV non-structural protein NS2B-NS3 protease with the last four amino acids of the NS2B cofactor bound at the NS3 active site. This structure represents a post-proteolysis state of the enzyme during viral polyprotein processing and provides insights into peptide substrate recognition by the protease. Nuclear magnetic resonance (NMR) studies and protease activity assays unravel the protein dynamics upon binding the protease inhibitor BPTI in solution and confirm this finding. The structural and functional insights of the ZIKV protease presented here should advance our current understanding of flavivirus replication and accelerate structure-based antiviral drug discovery against ZIKV. NMRC (Natl Medical Research Council, S’pore) Published version 2017-05-11T07:32:12Z 2019-12-06T15:10:29Z 2017-05-11T07:32:12Z 2019-12-06T15:10:29Z 2016 Journal Article Phoo, W. W., Li, Y., Zhang, Z., Lee, M. Y., Loh, Y. R., Tan, Y. B., et al. (2016). Structure of the NS2B-NS3 protease from Zika virus after self-cleavage. Nature Communications, 7, 13410-. 2041-1723 https://hdl.handle.net/10356/83027 http://hdl.handle.net/10220/42379 10.1038/ncomms13410 en Nature Communications © 2016 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 8 p. application/pdf |
| spellingShingle | Zika virus NS2B-NS3 Phoo, Wint Wint Li, Yan Zhang, Zhenzhen Lee, Michelle Yueqi Loh, Ying Ru Tan, Yaw Bia Ng, Elizabeth Yihui Lescar, Julien Kang, CongBao Luo, Dahai Structure of the NS2B-NS3 protease from Zika virus after self-cleavage |
| title | Structure of the NS2B-NS3 protease from Zika virus after self-cleavage |
| title_full | Structure of the NS2B-NS3 protease from Zika virus after self-cleavage |
| title_fullStr | Structure of the NS2B-NS3 protease from Zika virus after self-cleavage |
| title_full_unstemmed | Structure of the NS2B-NS3 protease from Zika virus after self-cleavage |
| title_short | Structure of the NS2B-NS3 protease from Zika virus after self-cleavage |
| title_sort | structure of the ns2b ns3 protease from zika virus after self cleavage |
| topic | Zika virus NS2B-NS3 |
| url | https://hdl.handle.net/10356/83027 http://hdl.handle.net/10220/42379 |
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