Home  |  Contact
PROSITE documentation PDOC51527 [for PROSITE entry PS51527]

Flavivirus NS2B and NS3 protease (NS3pro) domain profiles





Description

Pathogenic members of the flavivirus family [E1], including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The genome encodes three structural proteins found in the mature virion (C, prM, and E) and seven "nonstructural" (i.e., not part of the virion architecture) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). Full-length NS3 is a bifunctional protein. The N-terminal 175 residues comprise a chymotrypsin-like protease, "NS3pro", while the C-terminal portion is a helicase ("NS3hel"). The NS2B protein, which is located in the polypeptide precursor immediately upstream of the NS3pro domain, functions as the cofactor for NS3pro. A 35-48 residue central portion is required for protease activity in vitro, while N- and C-terminal flanking hydrophobic regions are predicted to anchor the NS2B-NS3 complex into the host endoplasmic reticulum membrane. The two component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication [1,2,3]. The NS3pro domain forms peptidase family S7 (flavivirin family) of clan PA [E2].

The NS3pro has a classical serine protease catalytic triad (His, Asp, and Ser). The enzymatic activity of NS3pro is enhanced by interacting with the central 40 amino acid of NS2B which acts as an essential cofactor. The NS3pro domain has an overall structure of two barrels made of six β sheets each, with the active site located in the cleft between the barrels. The NS2B hydrophilic core cofactor contributes one of the N-terminal β sheets (see <PDB:3L6P>) [1,2,3].

The profiles we developed cover the entire flavivirus NS2B and NS3pro domains.

Last update:

March 2011 / First entry.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

FLAVIVIRUS_NS2B, PS51527; Flavivirus NS2B domain profile  (MATRIX)

FLAVIVIRUS_NS3PRO, PS51528; Flavivirus NS3 protease (NS3pro) domain profile  (MATRIX)


References

1AuthorsAleshin A.E. Shiryaev S.A. Strongin A.Y. Liddington R.C.
TitleStructural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold.
SourceProtein Sci. 16:795-806(2007).
PubMed ID17400917
DOI10.1110/ps.072753207

2AuthorsWichapong K. Pianwanit S. Sippl W. Kokpol S.
TitleHomology modeling and molecular dynamics simulations of Dengue virus NS2B/NS3 protease: insight into molecular interaction.
SourceJ. Mol. Recognit. 23:283-300(2010).
PubMed ID19693793
DOI10.1002/jmr.977

3AuthorsChandramouli S. Joseph J.S. Daudenarde S. Gatchalian J. Cornillez-Ty C. Kuhn P.
TitleSerotype-specific structural differences in the protease-cofactor complexes of the dengue virus family.
SourceJ. Virol. 84:3059-3067(2010).
PubMed ID20042502
DOI10.1128/JVI.02044-09

E1Titlehttps://viralzone.expasy.org/24?outline=all_by_species
Source?

E2Titlehttps://www.ebi.ac.uk/merops/cgi-bin/famsum?family=S7
Source?



PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.

Miscellaneous

View entry in original PROSITE document format
View entry in raw text format (no links)