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Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni.

Andrade LF, Nahum LA, Avelar LG, Silva LL, Zerlotini A, Ruiz JC, Oliveira G - BMC Genomics (2011)

Bottom Line: The results show that S. mansoni has proteins in all ePK groups.None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite.Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches.

View Article: PubMed Central - HTML - PubMed

Affiliation: Genomics and Computational Biology Group, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, MG- 30190-002, Brazil.

ABSTRACT

Background: Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The Schistosoma mansoni genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the S. mansoni predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets.

Results: We have identified 252 ePKs, which corresponds to 1.9% of the S. mansoni predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that S. mansoni has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite. Only 16 S. mansoni ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite.

Conclusions: Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will highlight the biochemical and physiological adaptations of S. mansoni in response to diverse environments during the parasite development, vector interaction, and host infection.

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ePKinome in the predicted proteomes of diverse taxa. A total of 252 PKs were identified in the predicted proteome of S. mansoni. For comparison, the percentage (%) of the total predicted proteome that codes for kinases and the total number of ePKs (shown on top of each bar) is shown for four protozoan parasites: Pf - Plasmodium falciparum [107]; Tc - Trypanosoma cruzi, Tb - Trypanosoma brucei, Lm - Leishmania major [89]; two helminth parasites: Bm - Brugia malayi [108] and S. mansoni [26]; and five model organisms of KinBase Ce - Caernorhabditis elegans [51], Hm - Homo sapiens [13], Mm - Mus musculus [109], Dm - Drosophila melanogaster [110] and Sc - Saccharomyces cerevisiae [10].
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Figure 1: ePKinome in the predicted proteomes of diverse taxa. A total of 252 PKs were identified in the predicted proteome of S. mansoni. For comparison, the percentage (%) of the total predicted proteome that codes for kinases and the total number of ePKs (shown on top of each bar) is shown for four protozoan parasites: Pf - Plasmodium falciparum [107]; Tc - Trypanosoma cruzi, Tb - Trypanosoma brucei, Lm - Leishmania major [89]; two helminth parasites: Bm - Brugia malayi [108] and S. mansoni [26]; and five model organisms of KinBase Ce - Caernorhabditis elegans [51], Hm - Homo sapiens [13], Mm - Mus musculus [109], Dm - Drosophila melanogaster [110] and Sc - Saccharomyces cerevisiae [10].

Mentions: The ePK complement of S. mansoni, defined as the ePKinome, was identified by searching the parasite predict proteome with a HMM profile of the ePK catalytic domain of five selected organisms. This analysis revealed 252 ePKs in the S. mansoni predicted proteome, representing 1.9% of the total proteins encoded in the parasite genome. Although the total number of protein kinases found across the analyzed species varies greatly (from 82 to 503), the percentage values in respect to the genomes of protozoan and helminth parasites as well as other eukaryotes from KinBase range only between 1.5 to 2% (Figure 1).


Eukaryotic protein kinases (ePKs) of the helminth parasite Schistosoma mansoni.

Andrade LF, Nahum LA, Avelar LG, Silva LL, Zerlotini A, Ruiz JC, Oliveira G - BMC Genomics (2011)

ePKinome in the predicted proteomes of diverse taxa. A total of 252 PKs were identified in the predicted proteome of S. mansoni. For comparison, the percentage (%) of the total predicted proteome that codes for kinases and the total number of ePKs (shown on top of each bar) is shown for four protozoan parasites: Pf - Plasmodium falciparum [107]; Tc - Trypanosoma cruzi, Tb - Trypanosoma brucei, Lm - Leishmania major [89]; two helminth parasites: Bm - Brugia malayi [108] and S. mansoni [26]; and five model organisms of KinBase Ce - Caernorhabditis elegans [51], Hm - Homo sapiens [13], Mm - Mus musculus [109], Dm - Drosophila melanogaster [110] and Sc - Saccharomyces cerevisiae [10].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117856&req=5

Figure 1: ePKinome in the predicted proteomes of diverse taxa. A total of 252 PKs were identified in the predicted proteome of S. mansoni. For comparison, the percentage (%) of the total predicted proteome that codes for kinases and the total number of ePKs (shown on top of each bar) is shown for four protozoan parasites: Pf - Plasmodium falciparum [107]; Tc - Trypanosoma cruzi, Tb - Trypanosoma brucei, Lm - Leishmania major [89]; two helminth parasites: Bm - Brugia malayi [108] and S. mansoni [26]; and five model organisms of KinBase Ce - Caernorhabditis elegans [51], Hm - Homo sapiens [13], Mm - Mus musculus [109], Dm - Drosophila melanogaster [110] and Sc - Saccharomyces cerevisiae [10].
Mentions: The ePK complement of S. mansoni, defined as the ePKinome, was identified by searching the parasite predict proteome with a HMM profile of the ePK catalytic domain of five selected organisms. This analysis revealed 252 ePKs in the S. mansoni predicted proteome, representing 1.9% of the total proteins encoded in the parasite genome. Although the total number of protein kinases found across the analyzed species varies greatly (from 82 to 503), the percentage values in respect to the genomes of protozoan and helminth parasites as well as other eukaryotes from KinBase range only between 1.5 to 2% (Figure 1).

Bottom Line: The results show that S. mansoni has proteins in all ePK groups.None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite.Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches.

View Article: PubMed Central - HTML - PubMed

Affiliation: Genomics and Computational Biology Group, Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, MG- 30190-002, Brazil.

ABSTRACT

Background: Schistosomiasis remains an important parasitic disease and a major economic problem in many countries. The Schistosoma mansoni genome and predicted proteome sequences were recently published providing the opportunity to identify new drug candidates. Eukaryotic protein kinases (ePKs) play a central role in mediating signal transduction through complex networks and are considered druggable targets from the medical and chemical viewpoints. Our work aimed at analyzing the S. mansoni predicted proteome in order to identify and classify all ePKs of this parasite through combined computational approaches. Functional annotation was performed mainly to yield insights into the parasite signaling processes relevant to its complex lifestyle and to select some ePKs as potential drug targets.

Results: We have identified 252 ePKs, which corresponds to 1.9% of the S. mansoni predicted proteome, through sequence similarity searches using HMMs (Hidden Markov Models). Amino acid sequences corresponding to the conserved catalytic domain of ePKs were aligned by MAFFT and further used in distance-based phylogenetic analysis as implemented in PHYLIP. Our analysis also included the ePK homologs from six other eukaryotes. The results show that S. mansoni has proteins in all ePK groups. Most of them are clearly clustered with known ePKs in other eukaryotes according to the phylogenetic analysis. None of the ePKs are exclusively found in S. mansoni or belong to an expanded family in this parasite. Only 16 S. mansoni ePKs were experimentally studied, 12 proteins are predicted to be catalytically inactive and approximately 2% of the parasite ePKs remain unclassified. Some proteins were mentioned as good target for drug development since they have a predicted essential function for the parasite.

Conclusions: Our approach has improved the functional annotation of 40% of S. mansoni ePKs through combined similarity and phylogenetic-based approaches. As we continue this work, we will highlight the biochemical and physiological adaptations of S. mansoni in response to diverse environments during the parasite development, vector interaction, and host infection.

Show MeSH
Related in: MedlinePlus