National Center for
3H5X: Crystal Structure Of 2'-Amino-2'-Deoxy-Cytidine-5'-Triphosphate Bound To Norovirus Gii Rna Polymerase
Binding of 2'-amino-2'-deoxycytidine-5'-triphosphate to norovirus polymerase induces rearrangement of the active site
J. Mol. Biol. (2009) 390 p.10-16
Crystal structures of a genogroup II.4 human norovirus polymerase bound to an RNA primer-template duplex and the substrate analogue 2'-amino-2'-deoxycytidine-5'-triphosphate have been determined to 1.8 A resolution. The alteration of the substrate-binding site that is required to accommodate the 2'-amino group leads to a rearrangement of the polymerase active site and a disruption of the coordination shells of the active-site metal ions. The mode of binding seen for 2'-amino-2'-deoxycytidine-5'-triphosphate suggests a novel molecular mechanism of inhibition that may be exploited for the design of inhibitors targeting viral RNA polymerases.