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Open Access Research article

The TriTryp Phosphatome: analysis of the protein phosphatase catalytic domains

Rachel Brenchley12, Humera Tariq1, Helen McElhinney3, Balázs Szöőr3, Julie Huxley-Jones4, Robert Stevens2, Keith Matthews3 and Lydia Tabernero1*

Author Affiliations

1 Faculty of Life Sciences, Michael Smith, University of Manchester, M13 9PT, UK

2 Computer Science, University of Manchester, M13 9PT, UK

3 Institute of Immunology and Infection Research, University of Edinburgh, EH9 3JT, UK

4 GlaxoSmithKline Pharmaceuticals, Essex, CM19 5AW, UK

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BMC Genomics 2007, 8:434  doi:10.1186/1471-2164-8-434

Published: 26 November 2007

Abstract

Background

The genomes of the three parasitic protozoa Trypanosoma cruzi, Trypanosoma brucei and Leishmania major are the main subject of this study. These parasites are responsible for devastating human diseases known as Chagas disease, African sleeping sickness and cutaneous Leishmaniasis, respectively, that affect millions of people in the developing world. The prevalence of these neglected diseases results from a combination of poverty, inadequate prevention and difficult treatment. Protein phosphorylation is an important mechanism of controlling the development of these kinetoplastids. With the aim to further our knowledge of the biology of these organisms we present a characterisation of the phosphatase complement (phosphatome) of the three parasites.

Results

An ontology-based scan of the three genomes was used to identify 86 phosphatase catalytic domains in T. cruzi, 78 in T. brucei, and 88 in L. major. We found interesting differences with other eukaryotic genomes, such as the low proportion of tyrosine phosphatases and the expansion of the serine/threonine phosphatase family. Additionally, a large number of atypical protein phosphatases were identified in these species, representing more than one third of the total phosphatase complement. Most of the atypical phosphatases belong to the dual-specificity phosphatase (DSP) family and show considerable divergence from classic DSPs in both the domain organisation and sequence features.

Conclusion

The analysis of the phosphatome of the three kinetoplastids indicates that they possess orthologues to many of the phosphatases reported in other eukaryotes, including humans. However, novel domain architectures and unusual combinations of accessory domains, suggest distinct functional roles for several of the kinetoplastid phosphatases, which await further experimental exploration. These distinct traits may be exploited in the selection of suitable new targets for drug development to prevent transmission and spread of the diseases, taking advantage of the already extensive knowledge on protein phosphatase inhibitors.