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The TriTryp phosphatome: analysis of the protein phosphatase catalytic domains.

Brenchley R, Tariq H, McElhinney H, Szöor B, Huxley-Jones J, Stevens R, Matthews K, Tabernero L - BMC Genomics (2007)

Bottom Line: The prevalence of these neglected diseases results from a combination of poverty, inadequate prevention and difficult treatment.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Life Sciences, Michael Smith, University of Manchester, M13 9PT, UK. Rachel.Brenchley@postgrad.manchester.ac.uk

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.

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Comparison of the protein phosphatase complement in different genomes. Pie charts show the distribution of phosphatase catalytic domain genes in the different families: S/T Phosphatases, Protein tyrosine phosphatases, Dual-specificity phosphatases and PTEN/MTM lipid phosphatases. Phosphatase complements are shown for T. cruzi, T. brucei, L. major, in comparison with those for the Human [24, 26, 29, 128], S. cerevisiae [129, 130] and A. thaliana [76, 131] genomes. ACR2/cdc25-like are included in the DSP group.
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Figure 1: Comparison of the protein phosphatase complement in different genomes. Pie charts show the distribution of phosphatase catalytic domain genes in the different families: S/T Phosphatases, Protein tyrosine phosphatases, Dual-specificity phosphatases and PTEN/MTM lipid phosphatases. Phosphatase complements are shown for T. cruzi, T. brucei, L. major, in comparison with those for the Human [24, 26, 29, 128], S. cerevisiae [129, 130] and A. thaliana [76, 131] genomes. ACR2/cdc25-like are included in the DSP group.

Mentions: Following the ontology classification, a total of 252 protein phosphatases were identified: 86 in T. cruzi, 78 in T. brucei and 88 in L. major (full list in Additional file 1). Overall there is a great deal of similarity across the three genomes regarding the number of phosphatases of each type (Figure 1, Table 1). The three kinetoplastids have representatives from all the major families of phosphatases: STPs, PTPs, DSPs and the lipid phosphatases PTEN and Myotubularins. Missing genes include the low molecular weight PTP (LMW-PTP) and the eyes absent (EYA) phosphatase. Consistent with the evolutionary divergence of kinetoplastid parasites, a high proportion of phosphatases were identified that have no clear orthologues in other genomes reported to date. We found that atypical and kinetoplastid-specific phosphatases amount to 36% for T. cruzi, 39% for T. brucei and a 41% for L. major of the total of phosphatases, most of them belonging to the STP and DSP subfamilies (Table 1).


The TriTryp phosphatome: analysis of the protein phosphatase catalytic domains.

Brenchley R, Tariq H, McElhinney H, Szöor B, Huxley-Jones J, Stevens R, Matthews K, Tabernero L - BMC Genomics (2007)

Comparison of the protein phosphatase complement in different genomes. Pie charts show the distribution of phosphatase catalytic domain genes in the different families: S/T Phosphatases, Protein tyrosine phosphatases, Dual-specificity phosphatases and PTEN/MTM lipid phosphatases. Phosphatase complements are shown for T. cruzi, T. brucei, L. major, in comparison with those for the Human [24, 26, 29, 128], S. cerevisiae [129, 130] and A. thaliana [76, 131] genomes. ACR2/cdc25-like are included in the DSP group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2175518&req=5

Figure 1: Comparison of the protein phosphatase complement in different genomes. Pie charts show the distribution of phosphatase catalytic domain genes in the different families: S/T Phosphatases, Protein tyrosine phosphatases, Dual-specificity phosphatases and PTEN/MTM lipid phosphatases. Phosphatase complements are shown for T. cruzi, T. brucei, L. major, in comparison with those for the Human [24, 26, 29, 128], S. cerevisiae [129, 130] and A. thaliana [76, 131] genomes. ACR2/cdc25-like are included in the DSP group.
Mentions: Following the ontology classification, a total of 252 protein phosphatases were identified: 86 in T. cruzi, 78 in T. brucei and 88 in L. major (full list in Additional file 1). Overall there is a great deal of similarity across the three genomes regarding the number of phosphatases of each type (Figure 1, Table 1). The three kinetoplastids have representatives from all the major families of phosphatases: STPs, PTPs, DSPs and the lipid phosphatases PTEN and Myotubularins. Missing genes include the low molecular weight PTP (LMW-PTP) and the eyes absent (EYA) phosphatase. Consistent with the evolutionary divergence of kinetoplastid parasites, a high proportion of phosphatases were identified that have no clear orthologues in other genomes reported to date. We found that atypical and kinetoplastid-specific phosphatases amount to 36% for T. cruzi, 39% for T. brucei and a 41% for L. major of the total of phosphatases, most of them belonging to the STP and DSP subfamilies (Table 1).

Bottom Line: The prevalence of these neglected diseases results from a combination of poverty, inadequate prevention and difficult treatment.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Life Sciences, Michael Smith, University of Manchester, M13 9PT, UK. Rachel.Brenchley@postgrad.manchester.ac.uk

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.

Show MeSH
Related in: MedlinePlus