Ligand size is a major determinant of specificity in periplasmic oxyanion-binding proteins: the 1.2 angstrom resolution crystal structure of Azotobacter vinelandii ModA

Background: Periplasmic receptors constitute a diverse class of binding pro teins that differ widely in size, sequence and ligand specificity. Neverthe less, almost all of them display a common pla folding motif and have simila r tertiary structures consisting of two globular domains. The ligand is bou nd at the bottom of a deep cleft, which lies at the interface between these two domains. The oxyanion-binding proteins are notable in that they can di scriminate between very similar ligands. Results: Azotobacter vinelandii is unusual in that it possesses two peripla smic molybdate-binding proteins. The crystal structure of one of these with bound ligand has been determined at 1.2 Angstrom resolution. It superficia lly resembles the structure of sulphate-binding protein (SBP) from Salmonel la typhimurium and uses a similar constellation of hydrogen-bonding interac tions to bind its ligand, However, the detailed interactions are distinct f rom those of SEP and the more closely related molybdate-binding protein of Escherichia coli. Conclusions: Despite differences in the residues involved in binding, the v olumes of the binding pockets in the A. vinelandii and E. coli molybdate-bi nding proteins are similar and are significantly larger than that of SEP. W e conclude that the discrimination between molybdate and sulphate shown by these binding proteins is largely dependent upon small differences in the s izes of these two oxyanions.