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PDBsum entry 2jlv
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Hydrolase/RNA
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PDB id
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2jlv
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References listed in PDB file
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Key reference
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Title
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Insights into RNA unwinding and ATP hydrolysis by the flavivirus ns3 protein.
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Authors
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D.Luo,
T.Xu,
R.P.Watson,
D.Scherer-Becker,
A.Sampath,
W.Jahnke,
S.S.Yeong,
C.H.Wang,
S.P.Lim,
A.Strongin,
S.G.Vasudevan,
J.Lescar.
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Ref.
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Embo J, 2008,
27,
3209-3219.
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PubMed id
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Abstract
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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.
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