title: Crystal structure of unlinked NS2B-NS3 protease from Zika virus.
abstract: 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.
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building 03-07, 59 Nanyang Drive, Singapore 636921.|NTU Institute of Structural Biology, Nanyang Technological University, Experimental Medicine Building 06-01, 59 Nanyang Drive, Singapore 636921.
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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669.
authors.forename: Ying Ru
authors.initials: YR
authors.lastname: Loh
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building 03-07, 59 Nanyang Drive, Singapore 636921.|NTU Institute of Structural Biology, Nanyang Technological University, Experimental Medicine Building 06-01, 59 Nanyang Drive, Singapore 636921.|School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.
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.
authors.forename: Alvin W
authors.initials: AW
authors.lastname: Hung
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos, #03-01, Singapore 138669. cbkang@etc.a-star.edu.sg luodahai@ntu.edu.sg.
authors.forename: CongBao
authors.initials: C
authors.lastname: Kang
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Experimental Medicine Building 03-07, 59 Nanyang Drive, Singapore 636921. cbkang@etc.a-star.edu.sg luodahai@ntu.edu.sg.|NTU Institute of Structural Biology, Nanyang Technological University, Experimental Medicine Building 06-01, 59 Nanyang Drive, Singapore 636921.
authors.forename: Dahai
authors.initials: D
authors.lastname: Luo
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D009842:Oligopeptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D059748:Proteolysis; D020365:RNA Helicases / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry; D013379:Substrate Specificity; D017361:Viral Nonstructural Proteins / Q000737:chemistry*; D000071244:Zika Virus / Q000201:enzymology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D009842:Oligopeptides; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases