Site-Specific Glyco-Tagging of Native Proteins for the Development of Biologicals.

Glycosylation is an attractive approach to enhance biological properties of pharmaceutical proteins; however, the precise installation of glycans for structure-function studies remains challenging. Here, we describe a chemoenzymatic methodology for glyco-tagging of proteins by peptidoligase catalyzed modification of the -terminus of a protein with a synthetic glycopeptide ester having an -acetyl-glucosamine (GlcNAc) moiety to generate an -GlcNAc modified protein. The GlcNAc moiety can be elaborated into complex glycans by -glycosylation using well-defined sugar oxazolines and mutant forms of endo β--acetylglucosaminidases (ENGases).

Unveiling the GT114 family: Structural characterization of A075L, a glycosyltransferase from Paramecium bursaria chlorella virus-1 (PBCV-1).

Protein A075L is a β-xylosyltransferase that participates in producing the core of the N-glycans found in VP54, the major viral capsid protein of Paramecium bursaria chlorella virus-1 (PBCV-1). In this study, we present an X-ray crystallographic analysis of the apo form of A075L, along with its complexes with the sugar donor and with a trisaccharide acceptor. The protein structure shows a typical GT-B folding, with two Rossmann-like fold domains, in which the acceptor substrate binds to the N-terminal region, and the nucleotide-sugar donor binds to the C-terminal region.

Unprecedented selectivity for homologous lectin targets: differential targeting of the viral receptors L-SIGN and DC-SIGN.

DC-SIGN (CD209) and L-SIGN (CD209L) are two C-type lectin receptors (CLRs) that facilitate SARS-CoV-2 infections as viral co-receptors. SARS-CoV-2 manipulates both DC-SIGN and L-SIGN for enhanced infection, leading to interest in developing receptor antagonists. Despite their structural similarity (82% sequence identity), they function differently.