3U1I

Dengue virus protease covalently bound to a peptide

3U1I の概要

• エントリーDOI: 10.2210/pdb3u1i/pdb
• 関連するPDBエントリー: 3UIJ
• 関連するBIRD辞書のPRD_ID: PRD_000988
• 分子名称: Serine protease subunit NS2B, Serine protease NS3, peptide of (BEZ)(NLE)KR(OAR), ... (5 entities in total)
• 機能のキーワード: serine protease, er membrane, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Dengue virus 3 (DENV-3); 詳細
• 細胞内の位置: Capsid protein C: Virion (Potential). Peptide pr: Secreted (By similarity). Small envelope protein M: Virion membrane; Multi-pass membrane protein (By similarity). Envelope protein E: Virion membrane; Multi- pass membrane protein (By similarity). Non-structural protein 1: Secreted. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): Q5UB51 Q5UB51
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 53200.87

構造登録者

Noble, C.G. (登録日: 2011-09-29, 公開日: 2011-11-09, 最終更新日: 2023-11-15)

主引用文献

Noble, C.G.,Seh, C.C.,Chao, A.T.,Shi, P.Y.
Ligand-bound structures of the dengue virus protease reveal the active conformation
J.Virol., 86:438-446, 2012

PubMed Abstract: Dengue is a mosquito-borne viral hemorrhagic disease that is a major threat to human health in tropical and subtropical regions. Here we report crystal structures of a peptide covalently bound to dengue virus serotype 3 (DENV-3) protease as well as the serine-protease inhibitor aprotinin bound to the same enzyme. These structures reveal, for the first time, a catalytically active, closed conformation of the DENV protease. In the presence of the peptide, the DENV-3 protease forms the closed conformation in which the hydrophilic β-hairpin region of NS2B wraps around the NS3 protease core, in a manner analogous to the structure of West Nile virus (WNV) protease. Our results confirm that flavivirus proteases form the closed conformation during proteolysis, as previously proposed for WNV. The current DENV-3 protease structures reveal the detailed interactions at the P4' to P3 sites of the substrate. The new structural information explains the sequence preference, particularly for long basic residues in the nonprime side, as well as the difference in substrate specificity between the WNV and DENV proteases at the prime side. Structural analysis of the DENV-3 protease-peptide complex revealed a pocket that is formed by residues from NS2B and NS3; this pocket also exists in the WNV NS2B/NS3 protease structure and could be targeted for potential antivirus development. The structural information presented in the current study is invaluable for the design of specific inhibitors of DENV protease.

PubMed: 22031935
DOI: 10.1128/JVI.06225-11

実験手法

X-RAY DIFFRACTION (2.3 Å)