Crystal structure of mammalian purple acid phosphatase

Background: Mammalian purple acid phosphatases are highly conserved binucle ar metal-containing enzymes produced by osteoclasts, the cells that resorb bone. The enzyme is a target for drug design because there is strong eviden ce that it is involved in bone resorption. Results: The 1.55 Angstrom resolution structure of pig purple acid phosphat ase has been solved by multiple isomorphous replacement. The enzyme compris es two sandwiched beta sheets flanked by or-helical segments. The molecule shows internal symmetry, with the metal ions bound at the interface between the two halves. Conclusions: Despite less than 15% sequence identity, the protein fold rese mbles that of the catalytic domain of plant purple acid phosphatase and som e serine/threonine protein phosphatases. The active-site regions of the mam malian and plant purple acid phosphatases differ significantly, however. Th e internal symmetry suggests that the binuclear centre evolved as a result of the combination of mononuclear ancestors. The structure of the mammalian enzyme provides a basis for antiosteoporotic drug design.