2JLZ: Dengue Virus 4 Ns3 Helicase In Complex With Ssrna And Adp

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.
PDB ID: 2JLZDownload
MMDB ID: 68060
PDB Deposition Date: 2008/9/15
Updated in MMDB: 2008/11
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Dengue virus 4 Thailand/0348/1991
Similar Structures:
Biological Unit for 2JLZ: dimeric; determined by author and by software (PQS)
Molecular Components in 2JLZ
Label Count Molecule
Protein (1 molecule)
Serine Protease Subunit NS3
Molecule annotation
Nucleotide(1 molecule)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB