Tartrate-resistant acid phosphatase: A target for anti-osteoporotic chemotherapeutics

Vella, Peter, McGeary, Ross P., Gahan, Lawrence R. and Schenk, Gerhard (2010) Tartrate-resistant acid phosphatase: A target for anti-osteoporotic chemotherapeutics. Current Enzyme Inhibition, 6 3: 118-129. doi:10.2174/157340810793384133

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Author Vella, Peter
McGeary, Ross P.
Gahan, Lawrence R.
Schenk, Gerhard
Title Tartrate-resistant acid phosphatase: A target for anti-osteoporotic chemotherapeutics
Journal name Current Enzyme Inhibition   Check publisher's open access policy
ISSN 1573-4080
Publication date 2010-10
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/157340810793384133
Volume 6
Issue 3
Start page 118
End page 129
Total pages 12
Place of publication Bussum, The Netherlands
Publisher Bentham Science Publishers
Collection year 2011
Language eng
Subject 06 Biological Sciences
03 Chemical Sciences
Abstract Tartrate-resistant acid phosphatases (TRAcPs) belong to the family of binuclear metallohydrolases and catalyse the hydrolysis of a wide range of phosphomonoester and amide substrates. These enzymes have been characterised from numerous animal, plant and fungal sources. They are distinguished from other phosphatases by their resistance to inhibition by tartrate, their optimal catalytic efficiency at low pH and their characteristic purple colour, the latter due to an interaction between a conserved tyrosine residue in the active site and an Fe(III). Consequently, these enzymes are often referred to as purple acid phosphatases (PAPs). TRAcPs catalyse the hydrolysis of a range of substrates (including ATP) and are inhibited by the reaction product phosphate and related tetraoxo anions (i.e. molybdate, arsenate, vanadate), as well as fluoride. The interactions between these inhibitors and TRAcPs have been investigated with structural, kinetic and spectroscopic techniques, resulting in the proposal of a comprehensive eight-step reaction mechanism. In animals, TRAcP activity is directly linked to bone resorption; serum levels of the enzyme are therefore a main marker for the diagnosis of osteoporosis. Furthermore, high expression levels in macrophages during pathogen invasion indicate a pivotal role for TRAcPs in the immune response. TRAcP has thus emerged as a major target to develop chemotherapeutics to combat osteoporosis and other bone-related disorders. In this minireview, we will revisit recent developments in TRAcP inhibitor design and synthesis, and discuss how inhibitors have been pivotal in developing an increased understanding of the structure, function and mechanism of this enzyme.
Keyword Tartrate-resistant acid phosphatase
Purple Acid phosphatase
Bone metabolism
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
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Created: Tue, 21 Sep 2010, 12:52:05 EST by Laura McTaggart on behalf of School of Chemistry & Molecular Biosciences