Crystal structure of mammalian purple acid phosphatase

• Published in: Structure (London) 1999-07, Vol.7 (7), p.757-767
• Main Authors: Guddat, Luke W, McAlpine, Alan S, Hume, David, Hamilton, Susan, de Jersey, John, Martin, Jennifer L
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - chemistry; Acid Phosphatase - metabolism; Amino Acid Sequence; Animals; Binding Sites; Catalytic Domain; Crystallography, X-Ray; Glycoproteins - chemistry; Glycoproteins - metabolism; Humans; metalloenzyme; Models, Molecular; Molecular Sequence Data; Protein Conformation; protein structure; purple acid phosphatase; Sequence Homology, Amino Acid; Swine; tartrate-resistant acid phosphatase; uteroferrin
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/S0969-2126(99)80100-2

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 1.55Å resolution structure of pig purple acid phosphatase has been solved by multiple isomorphous replacement. The enzyme comprises two sandwiched β sheets flanked by α-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.