title: Structure of the NS2B-NS3 protease from Zika virus after self-cleavage.
abstract: 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.
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, EMB 03-07, 59 Nanyang Drive, Singapore 636921, Singapore.|School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 636921, Singapore.|NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
authors.forename: Wint Wint
authors.initials: WW
authors.lastname: Phoo
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis way, Nanos, #03-01, Singapore 138669, Singapore.
authors.forename: Yan
authors.identifier: 0000-0003-1963-839X
authors.initials: Y
authors.lastname: Li
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, EMB 03-07, 59 Nanyang Drive, Singapore 636921, Singapore.|NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis way, Nanos, #03-01, Singapore 138669, Singapore.
authors.forename: Michelle Yueqi
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis way, Nanos, #03-01, Singapore 138669, Singapore.
authors.forename: Ying Ru
authors.initials: YR
authors.lastname: Loh
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, EMB 03-07, 59 Nanyang Drive, Singapore 636921, Singapore.|NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
authors.forename: Yaw Bia
authors.initials: YB
authors.lastname: Tan
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis way, Nanos, #03-01, Singapore 138669, Singapore.
authors.forename: Elizabeth Yihui
authors.initials: EY
authors.lastname: Ng
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 636921, Singapore.|NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
authors.forename: Julien
authors.initials: J
authors.lastname: Lescar
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis way, Nanos, #03-01, Singapore 138669, Singapore.
authors.forename: CongBao
authors.identifier: 0000-0002-9886-9374
authors.initials: C
authors.lastname: Kang
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, EMB 03-07, 59 Nanyang Drive, Singapore 636921, Singapore.|School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 636921, Singapore.|NTU Institute of Structural Biology, Nanyang Technological University, EMB 06-01, 59 Nanyang Drive, Singapore 636921, Singapore.
authors.forename: Dahai
authors.identifier: 0000-0001-7637-7275
authors.initials: D
authors.lastname: Luo
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D059748:Proteolysis; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000378:metabolism*; D000071244:Zika Virus / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D010447:Peptide Hydrolases