BACKGROUND: Mammalian purple acid phosphatases are highly conserved binuclear metal-containing enzymes produced by osteoclasts, the cells that resorb bone. The enzyme is a target for drug design because there is strong evidence that it is involved in bone resorption. RESULTS: The 1.55 A resolution structure of pig purple acid phosphatase has been solved by multiple isomorphous replacement. The enzyme comprises two sandwiched beta sheets flanked by alpha-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 resembles that of the catalytic domain of plant purple acid phosphatase and some serine/threonine protein phosphatases. The active-site regions of the mammalian and plant purple acid phosphatases differ significantly, however. The 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.
BACKGROUND:Mammalian purple acid phosphatases are highly conserved binuclear metal-containing enzymes produced by osteoclasts, the cells that resorb bone. The enzyme is a target for drug design because there is strong evidence that it is involved in bone resorption. RESULTS: The 1.55 A resolution structure of pig purple acid phosphatase has been solved by multiple isomorphous replacement. The enzyme comprises two sandwiched beta sheets flanked by alpha-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 resembles that of the catalytic domain of plant purple acid phosphatase and some serine/threonine protein phosphatases. The active-site regions of the mammalian and plant purple acid phosphatases differ significantly, however. The 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.
Authors: Peter M Brown; Tom T Caradoc-Davies; James M J Dickson; Garth J S Cooper; Kerry M Loomes; Edward N Baker Journal: Proc Natl Acad Sci U S A Date: 2006-09-29 Impact factor: 11.205
Authors: Mauricio Lanznaster; Ademir Neves; Adailton J Bortoluzzi; Veronika V E Aires; Bruno Szpoganicz; Hernán Terenzi; Patricia Cardoso Severino; Julie M Fuller; Simon C Drew; Lawrence R Gahan; Graeme R Hanson; Mark J Riley; Gerhard Schenk Journal: J Biol Inorg Chem Date: 2005-04-21 Impact factor: 3.358
Authors: Colin J Jackson; Kieran S Hadler; Paul D Carr; Aaron J Oakley; Sylvia Yip; Gerhard Schenk; David L Ollis Journal: Acta Crystallogr Sect F Struct Biol Cryst Commun Date: 2008-07-05