2GGV

Crystal structure of the West Nile virus NS2B-NS3 protease, His51Ala mutant

2GGV の概要

• エントリーDOI: 10.2210/pdb2ggv/pdb
• 分子名称: non-structural protein 2B, non-structural protein 3 (3 entities in total)
• 機能のキーワード: beta barrel, serine protease, viral protease, flavivirus, hydrolase
• 由来する生物種: West Nile virus; 詳細
• 細胞内の位置: Envelope protein E: Virion membrane; Multi- pass membrane protein: Q203W3 Q203W3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26016.94

構造登録者

Aleshin, A.E.,Shiryaev, S.A.,Strongin, A.Y.,Liddington, R.C. (登録日: 2006-03-24, 公開日: 2007-03-27, 最終更新日: 2024-02-14)

主引用文献

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

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: 17400917
DOI: 10.1110/ps.072753207

実験手法

X-RAY DIFFRACTION (1.8 Å)