ATOMIC BASIS OF THE EXQUISITE SPECIFICITY OF PHOSPHATE AND SULFATE TRANSPORT RECEPTORS

We have determined, by the method of x-ray crystallography, the 1.7 An gstrom resolution three-dimensional structures of the ligand-bound for m of the phosphate receptor as well as the sulfate receptor. These pro tein structures provide an unprecedented atomic-level understanding of the mechanism governing the exquisite specificity of each receptor. A lthough they lack amino acid sequence homology, both receptors have ve ry similar three-dimensional structure. The structure consists of two globular domains separated by a deep cleft which contains the ligand-b inding site. The bound phosphate and sulfate are totally devoid of wat er of hydration. The bound phosphate is tightly held in place by 12 hy drogen bonds, 11 with donor and 1 with acceptor groups. The acceptor g roup (an Asp carboxylate side chain) plays three key roles. It confers specificity by directly recognizing one proton of either the monobasi c or dibasic phosphate. It also assists in the recognition of another proton of the monobasic phosphate. Finally, because of charge repulsio n, it disallows binding of fully ionized sulfate. The sulfate bound to the sulfate receptor makes seven hydrogen bonds with uncharged polar groups exclusively. The absence of an acceptor group in the binding si te of the sulfate receptor is not conducive to phosphate binding.