Structural basis for the function of Bacillus subtilis phosphoribosylpyrophosphate synthetase

Here we report the first three-dimensional structure of a phosphoribosylpyr ophosphate (PRPP) synthetase, PRPP is an essential intermediate in several biosynthetic pathways. structures of the Bacillus subtilis PRPP synthetase in complex with analogs of the activator phosphate and the allosteric inhib itor ADP show that the functional form of the enzyme is a hexamer, The indi vidual subunits fold into two domains, both of which resemble the type I ph osphoribosyltransfereases, The active site is located between the two domai ns and includes residues from two subunits, Phosphate and ADP bind to the s ame regulatory site consisting of residues from three subunits of the hexam er. In addition to identifying residues important for binding substrates an d effecters, the structures suggest a novel mode of allosteric regulation.