2IJO
Crystal Structure of the West Nile virus NS2B-NS3 protease complexed with bovine pancreatic trypsin inhibitor
Summary for 2IJO
| Entry DOI | 10.2210/pdb2ijo/pdb |
| Related | 2FOM 2FP7 2GGV |
| Descriptor | Polyprotein, Pancreatic trypsin inhibitor, ... (4 entities in total) |
| Functional Keywords | west nile virus, protease, aprotinin, bpti, ns2b, ns3, flavivirus, serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | West Nile virus More |
| Cellular location | Envelope protein E: Virion membrane; Multi- pass membrane protein: Q203W3 Q203W3 Secreted: P00974 |
| Total number of polymer chains | 3 |
| Total formula weight | 33512.57 |
| Authors | Aleshin, A.E.,Shiryaev, S.A.,Strongin, A.Y.,Liddington, R.C. (deposition date: 2006-09-29, release date: 2007-05-15, Last modification date: 2024-10-30) |
| Primary citation | Aleshin, A.E.,Shiryaev, S.A.,Strongin, A.Y.,Liddington, R.C. Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold. Protein Sci., 16:795-806, 2007 Cited by PubMed Abstract: Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The two-component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication. Here, we report the crystal structure of WNV NS2B-NS3pro both in a substrate-free form and in complex with the trypsin inhibitor aprotinin/BPTI. We show that aprotinin binds in a substrate-mimetic fashion in which the productive conformation of the protease is fully formed, providing evidence for an "induced fit" mechanism of catalysis and allowing us to rationalize the distinct substrate specificities of WNV and DV proteases. We also show that the NS2B cofactor of WNV can adopt two very distinct conformations and that this is likely to be a general feature of flaviviral proteases, providing further opportunities for regulation. Finally, by comparing the flaviviral proteases with the more distantly related Hepatitis C virus, we provide insights into the evolution of the Flaviviridae fold. Our work should expedite the design of protease inhibitors to treat a range of flaviviral infections. PubMed: 17400917DOI: 10.1110/ps.072753207 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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