Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus

Paul Erbel; Nikolaus Schiering; Allan D'Arcy; Martin Renatus; Markus Kroemer; Siew Pheng Lim; Zheng Yin; Thomas H Keller; Subhash G Vasudevan; Ulrich Hommel

doi:10.1038/nsmb1073

Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus

Nat Struct Mol Biol. 2006 Apr;13(4):372-3. doi: 10.1038/nsmb1073. Epub 2006 Mar 12.

Authors

Paul Erbel¹, Nikolaus Schiering, Allan D'Arcy, Martin Renatus, Markus Kroemer, Siew Pheng Lim, Zheng Yin, Thomas H Keller, Subhash G Vasudevan, Ulrich Hommel

Affiliation

¹ Novartis Institutes for Biomedical Research, Protease Platform, 4002 Basel, Switzerland.

PMID: 16532006
DOI: 10.1038/nsmb1073

Abstract

The replication of flaviviruses requires the correct processing of their polyprotein by the viral NS3 protease (NS3pro). Essential for the activation of NS3pro is a 47-residue region of NS2B. Here we report the crystal structures of a dengue NS2B-NS3pro complex and a West Nile virus NS2B-NS3pro complex with a substrate-based inhibitor. These structures identify key residues for NS3pro substrate recognition and clarify the mechanism of NS3pro activation.

MeSH terms

Binding Sites
Dengue Virus / enzymology*
Enzyme Activation
Hydrogen Bonding
Macromolecular Substances
Models, Molecular
Oligopeptides
Protease Inhibitors / chemistry
Protease Inhibitors / metabolism
RNA Helicases / chemistry
RNA Helicases / metabolism
Serine Endopeptidases / chemistry*
Serine Endopeptidases / metabolism*
Viral Nonstructural Proteins / chemistry*
Viral Nonstructural Proteins / metabolism*
West Nile virus / enzymology*

Substances

Macromolecular Substances
NS2B protein, flavivirus
NS3 protein, flavivirus
Oligopeptides
Protease Inhibitors
Viral Nonstructural Proteins
benzoyl-norleucyl-lysyl-arginyl-arginal
NS3 protease, dengue virus
Serine Endopeptidases
RNA Helicases

Associated data

PDB/1BEF
PDB/2FOM
PDB/2FP7