US EPA

1343805 

Journal Article 

The TriTryp Phosphatome: analysis of the protein phosphatase catalytic domains 

Brenchley, R; Tariq, H; Mcelhinney, H; Szoor, B; Huxley-Jones, J; Stevens, R; Matthews, K; Tabernero, L 

2007 

Yes 

BMC Genomics
ISSN: 1471-2164 

8 

18039372 

10.1186/1471-2164-8-434 

WOS:000252441600001 

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.