Crystal structure of ATP sulfurylase from Saccharomyces cerevisiae, a key enzyme in sulfate activation

ATP sulfurylases (ATPSs) are ubiquitous enzymes that catalyse the primary s tep of intracellular sulfate activation: the reaction of inorganic sulfate with ATP to form adenosine-5'-phosphosulfate (APS) and pyrophosphate (PPI). With the crystal structure of ATPS from the yeast Saccharomyces cerevisiae , we have solved the first structure of a member of the ATP sulfurylase fam ily, We have analysed the crystal structure of the native enzyme at 1.95 An gstrom resolution using multiple isomorphous replacement (MIR) and, subsequ ently, the ternary enzyme product complex with APS and PPI bound to the act ive site. The enzyme consists of six identical subunits arranged in two sta cked rings in a D3 symmetric assembly. Nucleotide binding causes significan t conformational changes, which lead to a rigid body structural displacemen t of domains III and IV of the ATPS monomer. Despite having similar folds a nd active site design, examination of the active site of ATPS and compariso n with known structures of related nucleotidylyl transferases reveal a nove l ATP binding mode that is peculiar to ATP sulfurylases.