3U1J

Aprotinin bound to Dengue virus protease

Summary for 3U1J

• Entry DOI: 10.2210/pdb3u1j/pdb
• Related: 3U1I
• Descriptor: Serine protease subunit NS2B, Serine protease NS3, Pancreatic trypsin inhibitor, ... (4 entities in total)
• Functional Keywords: serine protease, bovine pancreatic trypsin inhibitor, er membrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Dengue virus 3 (DENV-3); More
• Cellular location: 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; Secreted: P00974
• Total number of polymer chains: 3
• Total formula weight: 32272.02

Authors

Noble, C.G. (deposition date: 2011-09-30, release date: 2011-11-09, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.8 Å)