title: An inhibition model of BPTI to unlinked dengue virus NS2B-NS3 protease.
abstract: One approach to treating the dengue virus infection is to inhibit its NS2B-NS3 protease that plays a vital role in virus maturation. However, the lack of structural information on the active conformation of the protease hindered related drug design. With a co-expression system, we obtained the active two-component protease in its unlinked form. BPTI shows strong competitive inhibitory activity (Ki = 6.5 nM) against this unlinked protease, which adopts a closed conformation. Based on the biochemical and NMR perturbation information, an inhibition model of BPTI to NS2B-NS3 protease is proposed.
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China; Graduate University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Hou
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China. Electronic address: junfeng@hmfl.ac.cn.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: liu_jinsong@gibh.ac.cn.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
mesh_terms: D007611:Aprotinin / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D001667:Binding, Competitive; D003716:Dengue Virus / Q000201:enzymology*; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D000085242:Viral Proteases
chemical_list: D007611:Aprotinin; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; C504449:NS3 protease, dengue virus; D000085242:Viral Proteases
keywords: Bovine pancreatic trypsin inhibitor; Closed/active conformation; Dengue virus; NMR spectroscopy; NS2B-NS3 protease