Protein – Carbohydrate Recognition
Cyanovirin (CVN) like lectins represent a new class of anti-viral agents. Lectins are well known multifaceted carbohydrate-binding proteins that specifically recognize diverse sugar structures and mediate a variety of biological processes such as cell-cell and host-pathogen interactions, serum glycoprotein turnover and innate immune responses. Our long-term goal in this research area is to understand the molecular mechanisms and structural basis of high-affinity oligosaccharide recognition. In 1998, our laboratory solved the first solution structure of a cyanobacterial derived protein, CVN, that exhibited potent HIV-inactivating properties. The structure revealed a novel three-dimensional fold, distinct from any known lectin folds. Extensive biochemical and structural characterizations based on our initial results and primarily from our laboratory have now led to the categorization of a new structural class of lectins, with CVN as the class defining member, the so called CVNH family. Numerous atomic structures of other CVNH family members were solved by NMR or X-ray crystallography which by now has led to a comprehensive molecular understanding of this class of anti-viral lectins.
Following the discovery of CV-N, a growing number of lectins that bind to the high mannose glycans on gp120 have been found. We characterized several members of the OAA (Oscillatoria agardhii) family, which exhibit a compact, beta-barrel-like architecture that is very different from previously characterized lectin structures and unique among all available protein structures in the Protein Data Bank (PDB). Most importantly, the carbohydrate recognition of Man-9 is also unique when compared with all other anti-viral lectins.