Abstract
BackgroundTartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics.FindingsA new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine.ConlusionThe gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.
Highlights
Tartrate-resistant acid phosphatases (TRAcPs), known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi
Related gene products from other eukaryotes were identified in the NCBI Homologene database http:// www.ncbi.nlm.nih.gov/sites/entrez?db=homologene and ENSEMBL resources http://www.ensembl.org, and included Bos taurus (NP_001026941) Pan troglodytes (XP_001145620), Canis familiaris (XP_536969), Mus musculus (NP_666179), Rattus norvegicus (NP_001013985), Gallus gallus (XP_414732) and Plasmodium falciparum (XP_001348209) indicating that this new gene product is evolutionarily conserved
The new human sequence was used to query the nr database to search for the closest relative with known structure, and identified the catalytic domain of TRAcPs from red kidney bean (P. vulgaris), 4KBP [6], and sweet potato (I. batatas), 1XZW [8]
Summary
Purple acid phosphatases (PAPs) are a diverse group of metalloenzymes that catalyse the hydrolysis of phosphate esters and anhydrides [1]. The X-ray crystal structures of TRAcPs from several sources, including human, pig, red kidney bean and sweet potato have been determined [6,7,8,9] Their sequence identity is only < 20%, these enzymes have a common core structure with five motifs that contain the invariant seven metal coordinating amino acids in the catalytic site [2]. A number of distinct TRAcP isoforms were identified in plants and bacteria, clearly illustrating the existence of multiple TRAcP genes in different kingdoms [1,2]. This is further supported by the existence of a plantlike TRAcP in animals [1]. We have extended our previous work on investigation of TRAcP and TRAcPlike protein content in animal genomes and identified a new gene product that is a remote homolog to both TRAcPs and Ser/ Thr protein phosphatases
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