The dengue virus NS2B-NS3 protease retains the closed conformation in the complex with BPTI.

Autor: Chen WN; Australian National University, Research School of Chemistry, Canberra, ACT 0200, Australia., Loscha KV; Australian National University, Research School of Chemistry, Canberra, ACT 0200, Australia., Nitsche C; Medicinal Chemistry, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany., Graham B; Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia., Otting G; Australian National University, Research School of Chemistry, Canberra, ACT 0200, Australia. Electronic address: gottfried.otting@anu.edu.au.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2014 Jun 27; Vol. 588 (14), pp. 2206-11. Date of Electronic Publication: 2014 May 21.
DOI: 10.1016/j.febslet.2014.05.018
Abstrakt: The C-terminal β-hairpin of NS2B (NS2Bc) in the dengue virus NS2B-NS3 protease is required for full enzymatic activity. In crystal structures without inhibitor and in the complex with bovine pancreatic trypsin inhibitor (BPTI), NS2Bc is displaced from the active site. In contrast, nuclear magnetic resonance (NMR) studies in solution only ever showed NS2Bc in the enzymatically active closed conformation. Here we demonstrate by pseudocontact shifts from a lanthanide tag that NS2Bc remains in the closed conformation also in the complex with BPTI. Therefore, the closed conformation is the best template for drug discovery.
(Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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