Domain

Flavivirus non-structural protein NS2B (IPR000487)

Short name: Flavi_NS2B

Domain relationships

None.

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 [PMID: 17400917, PMID: 19693793, PMID: 20042502]. 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 beta sheets each, with the active site located in the cleft between the barrels. The NS2B hydrophilic core cofactor contributes one of the N-terminal beta sheets [PMID: 17400917, PMID: 19693793, PMID: 20042502].

This entry represents a domain cover the entire flavivirus NS2B and NS3pro domains.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0004252 serine-type endopeptidase activity

Cellular Component

GO:0019012 virion

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
Pfam
PROSITE profiles