An inhibition model of BPTI to unlinked dengue virus NS2B‐NS3 protease. Issue 17 (12th June 2014)

• Record Type: Journal Article
• Authors: Li, Hua; Zhu, Lei; Hou, Shulin; Yang, Jing; Wang, Junfeng; Liu, Jinsong
• Is Part Of: FEBS letters. Volume 588:Issue 17(2014)
• Page Start: 2794
• Page End: 2799
• Publication Date: 2014-06-12
• Subjects: Dengue virus -- NS2B-NS3 protease -- Bovine pancreatic trypsin inhibitor -- NMR spectroscopy -- Closed/active conformation; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.05.063
• Languages: English
• ISSNs: 0014-5793

Abstract

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 ( K i = 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. Abstract : A new unlinked dengue NS2B‐NS3p was obtained in closed conformation. BPTI competitively inhibits the proteolytic activity of the unlinked protease. BPTI binding sites on NS2B‐NS3p were mapped out by chemical shift perturbations.