STRANGE BEDFELLOWS - INTERACTIONS BETWEEN ACIDIC SIDE-CHAINS IN PROTEINS

The oxygen atoms of two acidic side-chains are frequently found within hydrogen-bonding distance of each other in proteins. Two distinct typ es of cases are common. In metal-binding sites, the oxygen atoms are b rought near (average closest approach 3.0 Angstrom) by their common ro le as metal ligands. In a different location, either buried or on the protein surface, the two acidic groups can share a proton. The corresp onding O-O distances in the latter case are shorter (usually 2.7 Angst rom or less), and the geometry is typical of hydrogen-bonding interact ions. The glucose/galactose-binding protein of Salmonella typhimurium provides an example of a well-ordered Asp-Glu pair on the surface of a protein with a very short O-O distance, at a pH of 7.0. Other instanc es have been found at pH values as high as 8.0, suggesting substantial alteration of the pK(a) involved. These observations have implication s for the study of enzymes that use Fairs of acidic residues in bindin g and catalysis.