2JLR

Dengue virus 4 NS3 helicase in complex with AMPPNP

Summary for 2JLR

• Entry DOI: 10.2210/pdb2jlr/pdb
• Related: 2JLQ 2JLS 2JLU 2JLV 2JLW 2JLX 2JLY 2JLZ
• Descriptor: SERINE PROTEASE SUBUNIT NS3, MANGANESE (II) ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: ribonucleoprotein, nucleotide-binding, helicase, protease, hydrolase, atp analog, transferase, viral nucleoprotein, endoplasmic reticulum, cleavage on pair of basic residues, multifunctional enzyme, transcription regulation, nucleotidyltransferase, ns3 helicase structure, virion, atpase, nucleus, membrane, secreted, atp-binding, rna-binding, flaviviruses, glycoprotein, rna-directed rna polymerase, rna replication, serine protease, envelope protein, dengue virus, metal-binding, transmembrane, transcription, phosphoprotein, capsid protein
• Biological source: DENGUE VIRUS 4
• 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): Q2YHF0
• Total number of polymer chains: 1
• Total formula weight: 51914.61

Authors

Luo, D.H.,Xu, T.,Watson, R.P.,Becker, D.S.,Sampath, A.,Jahnke, W.,Yeong, S.S.,Wang, C.H.,Lim, S.P.,Vasudevan, S.G.,Lescar, J. (deposition date: 2008-09-15, release date: 2008-11-25, Last modification date: 2023-12-13)

Primary citation

Luo, D.,Xu, T.,Watson, R.P.,Scherer-Becker, D.,Sampath, A.,Jahnke, W.,Yeong, S.S.,Wang, C.H.,Lim, S.P.,Strongin, A.,Vasudevan, S.G.,Lescar, J.
Insights Into RNA Unwinding and ATP Hydrolysis by the Flavivirus Ns3 Protein.
Embo J., 27:3209-, 2008

PubMed Abstract: Together with the NS5 polymerase, the NS3 helicase has a pivotal function in flavivirus RNA replication and constitutes an important drug target. We captured the dengue virus NS3 helicase at several stages along the catalytic pathway including bound to single-stranded (ss) RNA, to an ATP analogue, to a transition-state analogue and to ATP hydrolysis products. RNA recognition appears largely sequence independent in a way remarkably similar to eukaryotic DEAD box proteins Vasa and eIF4AIII. On ssRNA binding, the NS3 enzyme switches to a catalytic-competent state imparted by an inward movement of the P-loop, interdomain closure and a change in the divalent metal coordination shell, providing a structural basis for RNA-stimulated ATP hydrolysis. These structures demonstrate for the first time large quaternary changes in the flaviviridae helicase, identify the catalytic water molecule and point to a beta-hairpin that protrudes from subdomain 2, as a critical element for dsRNA unwinding. They also suggest how NS3 could exert an effect as an RNA-anchoring device and thus participate both in flavivirus RNA replication and assembly.

PubMed: 19008861
DOI: 10.1038/EMBOJ.2008.232

Experimental method

X-RAY DIFFRACTION (2 Å)