Protein Domain : Flavivirus NS3, petidase S7 IPR001850

Type	Domain
Description	The viral genome of Flavivirus is a positive strand RNA that encodes a single polyprotein precursor. Processing of the polyprotein precursor into mature proteins is carried out by the host signal peptidase and by NS3 serine protease, which requires NS2B ( ) as a cofactor. Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are nospecific 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, while the C-terminal portionis a helicase. The NS2B protein, which is located in the polypeptide precursor immediately upstream of the NS3 protease domain, functions as the cofactor for NS3 protease. A 35-48 residue central portion is required forprotease activity in vitro, while N- and C-terminal flanking hydrophobic regions are predicted to anchor the NS2B-NS3 complex into the host endoplasmicreticulum membrane. The two component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is requiredfor viral replication [ , , ]. The NS3 protease forms the MEROPS peptidase family S7 (flavivirin family), clan PA.The NS3 protease has a classical serine protease catalytic triad (His, Asp, and Ser). The enzymatic activity is enhanced by interacting with thecentral 40 amino acid of NS2B which acts as an essential cofactor. The NS3 protease 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 [, , ].
Short Name	Flavivirus_NS3_S7