3RC5

Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease

3RC5 の概要

• エントリーDOI: 10.2210/pdb3rc5/pdb
• 関連するPDBエントリー: 3RC4 3RC6
• 分子名称: NS3/4A protease, Product MAVS, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: drug resistance, drug design, protease inhibitors, serine protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Hepatitis C virus subtype 1a; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22631.86

構造登録者

Schiffer, C.A.,Romano, K.P. (登録日: 2011-03-30, 公開日: 2011-05-04, 最終更新日: 2024-10-30)

主引用文献

Romano, K.P.,Laine, J.M.,Deveau, L.M.,Cao, H.,Massi, F.,Schiffer, C.A.
Molecular mechanisms of viral and host cell substrate recognition by hepatitis C virus NS3/4A protease.
J.Virol., 85:6106-6116, 2011

PubMed Abstract: Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.

PubMed: 21507982
DOI: 10.1128/JVI.00377-11

実験手法

X-RAY DIFFRACTION (1.6 Å)