Abstract: The binding mode of the antiviral compounds have been characterized through a variety of biophysical and structural studies, elaborating on the proposed aggregation mechanism of action. We demonstrate the direct binding of these antiviral compounds to NP using thermal shift enhancement assay (TSE) and NMR. In addition, we have completed a detailed analysis of the oligomerization mechanism of action using dynamic light scattering, analytical ultracentrifugation, and surface plasmon resonance (SPR). Structure determination using x-ray crystallography confirmed the proposed compound-induced oligomerization mechanism of action. The co-crystal structure revealed that two compounds bound in an anti-parallel fashion bridging two NP monomers, inducing a novel non-native NP oligomer.

Abstract: The present invention provides machine readable media embedded with the three-dimensional molecular structure coordinates of ATP phosphoribosyltransferase, and subsets thereof, including binding pockets, methods of using the structure to identify and design affecters, including inhibitors and activator, mutants of ATP-PRT, and compounds and compositions that affect ATP-PRT activity.