N-terminal region of NS3 and its cofactor NS2B constitute the protease. To function as an active enzyme, the NS3 protease requires the NS2B cofactor. NS2B is an integral membrane protein of 14 kDa that contains three domains: two trans-membrane segments located at the N- and C-termini and a central region of 47 amino acids (spanning amino-acids 49-96) that acts as an essential protein cofactor of the NS3 protease
structure-based identification of key residues and binding sites for inhibitor binding, design of non-competitive inhibitors for Dengue virus type 3 NS2b-NS3-protease, overview. The identified residues include 1. amino acids close to the beta sheet-loop-beta sheet known to be important in its closed conformation for NS2b 2. residues close to the active site, 3. several residues evenly spread on the NS2b-NS3 contact surface, and 4. some inner residues most likely related to the overall stability of the protease. Computational alanine scanning mutagenesis and similarity analysis based on sequence and structure homology, modeling. On the DENV NS3 protease, the residues Tyr23, Gly37, Phe46, Thr48, His51, Thr53, Leu58, Asp75, Tyr79, Trp89, and Thr156 are identified as class A and as the eleven highest ranked residues by both MLP models
the flavivirus NS3 protein is associated with the endoplasmic reticulum membrane via its close interaction with the central hydrophilic region of the NS2B integral membrane protein
the N-terminal region of NS3 and its cofactor NS2B constitute the protease that cleaves the viral polyprotein. The NS3 C-terminal domain possesses RNA helicase, nucleoside and RNA triphosphatase activities and is involved both in viral RNA replication and virus particle formation. NS2B-NS3 protein plays multiple roles in the virus life cycle. NS2B-NS3 serves as a hub for the assembly of the flavivirus replication complex and also modulates viral pathogenesis and the host immune response
Bessaud, M.; Pastorino, B.A.; Peyrefitte, C.N.; Rolland, D.; Grandadam, M.; Tolou, H.J.
Functional characterization of the NS2B/NS3 protease complex from seven viruses belonging to different groups inside the genus Flavivirus
Virus Res.
120
79-90
2006
Yellow fever virus, Zika virus, Saint Louis encephalitis virus, Bussuquara virus, Langat virus (P29837), Dengue virus type 3 (Q6YMS4), dengue virus type I (Q91NH1), Yellow fever virus Asibi, Dengue virus type 3 Sri Lanka/1266/2000 (Q6YMS4), dengue virus type I D1/H/IMTSSA/98/606 (Q91NH1), Langat virus TP21 (P29837), Zika virus Ar-D-41644, Saint Louis encephalitis virus MSI-7