Before our study, the crystal structures of the HBGA binding interfaces of three GI NoVs, the GI.1 NV, the GI.2 FUV and the GI.7 TCH, have been determined (Bu et al., 2008; Choi et al., 2008; Kubota et al., 2012; Shanker et al., 2014), providing valuable information for basic understanding of GI NoV-HBGA interactions.
The genetic and evolutionary relationships of GII huNoVs under selection by the host HBGAs have been well elucidated via a number of structural studies; however, such relationships among GI NoVs remain less clear due to the fact that the structures of HBGA-binding interfaces of only three GI NoVs with similar binding profiles are known.
Consequently, a pharma-interface is constructed based on the conserved binding interfaces of polypharmacological targets.
Structural comparison of the HBGA-binding interfaces of the two noroviruses has revealed shared features but significant differences in the location, sequence composition, and HBGA-binding modes.
The HBGA-binding interfaces of the two major genogroups of human noroviruses share some similarity in the overall structure and location; both are located in the outermost P2 regions of the capsids [13], [14], [15] and both are composed of three major structural components, corresponding to the bottom and the walls of the binding pocket (Fig. 1).
The conformational binding interface of BV is composed of two major areas, a β-Gal binding site and a Le epitope binding site, formed by ten amino acids from 3 (P-, T-, and S-) loop regions (Fig. 5).
The binding interface of L7Ae-related proteins comprises two elements.
The CBP binding interface of TDG is split into two distinct regions, one located in the N-terminus and including the regulatory domain, which is known to be essential for G T but not G U DNA repair activity [31], and the other located C-terminally [13].
The data showed that BV has a unique HBGA binding interface consisting of two major saccharide binding sites, each interacting with the β-1,3 Gal and the Le epitope.
A protein binding interface composes of two relatively large, spatially close protein surfaces with good geometric shape and chemical complementarity.
Thus, the same binding patch on the PRL-R ECD recognizes two distinct binding interfaces on each of two different hormones, yet each hormone activates a distinct biological outcome.
