Crystal structures of Norwalk virus polymerase bound to an RNA primer-template duplex
and either the natural substrate CTP or the inhibitor 5-nitrocytidine triphosphate
have been determined to 1.8Å resolution. These structures reveal a closed conformation
of the polymerase that differs significantly from previously determined open structures
of calicivirus and picornavirus polymerases. These closed complexes are trapped immediately
prior to the nucleotidyl transfer reaction, with the triphosphate group of the nucleotide
bound to two manganese ions at the active site, poised for reaction to the 3′-hydroxyl
group of the RNA primer. The positioning of the 5-nitrocytidine triphosphate nitro
group between the α-phosphate and the 3′-hydroxyl group of the primer suggests a novel,
general approach for the design of antiviral compounds mimicking natural nucleosides
and nucleotides.
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Article Info
Publication History
Received in revised form:
December 13,
2007
Received:
November 21,
2007
Footnotes
The atomic coordinates and structure factors (code 3BSN and 3BSO) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
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© 2008 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.
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