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PDBsum entry 1a1v
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Hydrolase/DNA
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PDB id
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1a1v
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Hepatitis c virus ns3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding.
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Authors
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J.L.Kim,
K.A.Morgenstern,
J.P.Griffith,
M.D.Dwyer,
J.A.Thomson,
M.A.Murcko,
C.Lin,
P.R.Caron.
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Ref.
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Structure, 1998,
6,
89.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Hepatitis C virus (HCV) represents a major health concern as it is
responsible for a significant number of hepatitis cases worldwide. Much research
has focused on the replicative enzymes of HCV as possible targets for more
effective therapeutic agents. HCV NS3 helicase may provide one such suitable
target. Helicases are enzymes which can unwind double-stranded regions of DNA or
RNA in an ATP-dependent reaction. The structures of several helicases have been
published but the structural details as to how ATP binding and hydrolysis are
coupled to RNA unwinding are unknown. RESULTS: The structure of the HCV NS3 RNA
helicase domain complexed with a single-stranded DNA oligonucleotide has been
solved to 2.2 A resolution. The protein consists of three structural domains
with the oligonucleotide lying in a groove between the first two domains and the
third. The first two domains have an adenylate kinase like fold, including a
phosphate-binding loop in the first domain. CONCLUSIONS: HCV NS3 helicase is a
member of a superfamily of helicases, termed superfamily II. Residues of NS3
helicase which are conserved among superfamily II helicases line an interdomain
cleft between the first two domains. The oligonucleotide binds in an orthogonal
binding site and contacts relatively few conserved residues. There are no strong
sequence-specific interactions with the oligonucleotide bases.
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Figure 7.
Figure 7. Helicase mechanism schematic. The binding of
polynucleotide by NS3 helicase in the absence of ATP leaves a
large cleft between domains 1 and 2. Binding of ATP occurs with
the b-phosphate binding to residues in motif I (GSGKT) and the
g-phosphate with Mg2+ binding to the conserved acidic residues
in motif II (DECH). This results in the closing of the
interdomain cleft and the binding of conserved arginines in
motif VI (QRRGRTGR) to the ATP phosphates. Val432 and Trp501
disrupt base stacking at either end of the single-stranded
region. Closure of the interdomain cleft leads to translocation
of the single strand in the 5' to 3' direction and forces
several bases to slip past Trp501. Hydrolysis of ATP facilitates
opening of the cleft and release of ADP. The orientation of
Trp501 favors movement of the polynucleotide in only one
direction such that opening of the gap results in net movement
of the helicase in a 3' ->5' direction.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1998,
6,
89-0)
copyright 1998.
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