Spotlights on Recent JACS Publications

■ SECRETS OF PROTEIN−POLYSACCHARIDE INTERACTIONS REVEALED Textbook descriptions of protein−ligand interactions generally feature high affinities and rigid substrates. But not all macromolecular complexes form that way. Case in point: the bacteriophage Sf6 tailspike protein (Sf6TSP), a trimeric enzyme that binds and cleaves long, floppy O-antigen polysaccharide chains on the surface of its bacterial host. Stefanie Barbirz, Mark Santer, and colleagues blend X-ray crystallography, NMR spectroscopy, surface plasmon resonance, and a new approach to model ligand interaction obtained from NMR spectroscopy called CORCEMA-ST-CSD, to study the interaction of the Sf6TSP complex with its ligands, including an octasaccharide, dodecasaccharide, and longer lipopolysaccharides (DOI: 10.1021/jacs.6b00240). The researchers’ analysis suggests that O-polysaccharides bind Sf6TSP via a long, shallow binding pocket capable of simultaneously holding up to eight sugar residues (two tetrameric repeats) via key hydrogen bonds, hydration, and hydrophobic interactions, with additional residues draped outside the pocket. The ligand is tightly bound and relatively rigid at one end of the catalytic site, but more dynamic near the other, reducing end. This multidisciplinary approach, the authors conclude, “could be a valuable scheme in other cases of weakly binding polysaccharide−protein complexes, where the extrapolation toward long polysaccharide fragments with computational methods is desired.” Jeffrey M. Perkel