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    Crystal structures of a purple acid phosphatase, representing different steps of this enzyme's catalytic cycle

    Schenk, Gerhard and Elliott, Tristan W. and Leung, Eleanor and Carrington, Lyle E. and Mitic, Natasa and Gahan, Lawrence R. and Guddat, Luke W. (2008) Crystal structures of a purple acid phosphatase, representing different steps of this enzyme's catalytic cycle. BMC Structural Biology, 8 (6). doi:10.1186/1472-6807. ISSN 1472-6807

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    Background: Purple acid phosphatases belong to the family of binuclear metallohydrolases and are involved in a multitude of biological functions, ranging from bacterial killing and bone metabolism in animals to phosphate uptake in plants. Due to its role in bone resorption purple acid phosphatase has evolved into a promising target for the development of anti-osteoporotic chemotherapeutics. The design of specific and potent inhibitors for this enzyme is aided by detailed knowledge of its reaction mechanism. However, despite considerable effort in the last 10 years various aspects of the basic molecular mechanism of action are still not fully understood. Results: Red kidney bean purple acid phosphatase is a heterovalent enzyme with an Fe(III)Zn(II) center in the active site. Two new structures with bound sulfate (2.4 Å) and fluoride (2.2 Å) provide insight into the pre-catalytic phase of its reaction cycle and phosphorolysis. The sulfate-bound structure illustrates the significance of an extensive hydrogen bonding network in the second coordination sphere in initial substrate binding and orientation prior to hydrolysis. Importantly, both metal ions are five-coordinate in this structure, with only one nucleophilic μ-hydroxide present in the metal-bridging position. The fluoride-bound structure provides visual support for an activation mechanism for this μ-hydroxide whereby substrate binding induces a shift of this bridging ligand towards the divalent metal ion, thus increasing its nucleophilicity. Conclusion: In combination with kinetic, crystallographic and spectroscopic data these structures of red kidney bean purple acid phosphatase facilitate the proposal of a comprehensive eight-step model for the catalytic mechanism of purple acid phosphatases in general.

    Item Type: Article
    Additional Information: This article is available from: © 2008 Schenk et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Keywords: Crystal structures; purple acid phosphatase; enzymes; catalytic cycle; binuclear metallohydrolases; anti-osteoporotic chemotherapeutics;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 3669
    Identification Number:
    Depositing User: Gary Schenk
    Date Deposited: 16 May 2012 15:14
    Journal or Publication Title: BMC Structural Biology
    Publisher: BioMed Central
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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