ISOMORPHOUS BINDING OF MERCURY-SUBSTITUTED THIOSACCHARIDES TO PERTUSSIS TOXIN CRYSTALS YIELDS CRYSTALLOGRAPHIC PHASES

An isomorphous derivative of pertussis toxin crystals was prepared usi ng a 2-alpha-mercuric analog of N-acetyl neuraminic acid in a method a nalogous to the use of inhibitors labelled with heavy atoms to solve c rystal structures of enzymes. This derivative exploits the specific bi nding between pertussis toxin and terminal sialic acid residues on rec eptor glycoproteins. Difference Patterson maps yielded heavy-atom site s which refined with good statistics, indicating that the protein prob ably does not undergo a conformational change on receptor binding. Mer curic analogs of other monosaccharides should be easily obtainable usi ng the same synthetic strategy, suggesting a general method for deriva tizing crystals of carbohydrate-binding proteins.