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Genome wide in silico analysis of Plasmodium falciparum phosphatome.

Pandey R, Mohmmed A, Pierrot C, Khalife J, Malhotra P, Gupta D - BMC Genomics (2014)

Bottom Line: Analysis of proteins expression profiles of the 67 phosphatases revealed that 44 phosphatases are expressed in both schizont as well as gametocytes stages.In the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes.Intriguingly, amongst these phosphatases, we could identify six Plasmodium specific phosphatases and 33 putative phosphatases that do not have human orthologs, thereby suggesting that these phosphatases have the potential to be explored as novel antimalarial drug targets.

View Article: PubMed Central - PubMed

Affiliation: Structural and Computational Biology group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. jamal.khalife@pasteur-lille.fr.

ABSTRACT

Background: Eukaryotic cellular machineries are intricately regulated by several molecular mechanisms involving transcriptional control, post-translational control and post-translational modifications of proteins (PTMs). Reversible protein phosphorylation/dephosphorylation process, which involves kinases as well as phosphatases, represents an important regulatory mechanism for diverse pathways and systems in all organisms including human malaria parasite, Plasmodium falciparum. Earlier analysis on P. falciparum protein-phosphatome revealed presence of 34 phosphatases in Plasmodium genome. Recently, we re-analysed P. falciparum phosphatome aimed at identifying parasite specific phosphatases.

Results: Plasmodium database (PlasmoDB 9.2) search, combined with PFAM and CDD searches, revealed 67 candidate phosphatases in P. falciparum. While this number is far less than the number of phosphatases present in Homo sapiens, it is almost the same as in other Plasmodium species. These Plasmodium phosphatase proteins were classified into 13 super families based on NCBI CDD search. Analysis of proteins expression profiles of the 67 phosphatases revealed that 44 phosphatases are expressed in both schizont as well as gametocytes stages. Fourteen phosphatases are common in schizont, ring and trophozoite stages, four phosphatases are restricted to gametocytes, whereas another three restricted to schizont stage. The phylogenetic trees for each of the known phosphatase super families reveal a considerable phylogenetic closeness amongst apicomplexan organisms and a considerable phylogenetic distance with other eukaryotic model organisms included in the study. The GO assignments and predicted interaction partners of the parasite phosphatases indicate its important role in diverse cellular processes.

Conclusion: In the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes. Intriguingly, amongst these phosphatases, we could identify six Plasmodium specific phosphatases and 33 putative phosphatases that do not have human orthologs, thereby suggesting that these phosphatases have the potential to be explored as novel antimalarial drug targets.

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Summary of protein phosphatomes of model organisms selected for the comparative studies.
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Fig1: Summary of protein phosphatomes of model organisms selected for the comparative studies.

Mentions: Using the computational methods described in the Methods section, we collected and screened the predicted proteomes of Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi, Plasmodium cynomolgi, Plasmodium berghei, Plasmodium chabaudi, Eimeria tenella, Toxoplasma gondii, Babesia bovis, Theileria parva, Cryptosporidium parvam, Escherichia coli, Arabidopsis thaliana, Saccharomyces cerevisiae and Homo sapiens for phosphatase sequences. We used text search as well as complete proteome of P. falciparum and for others organisms only text search was performed to retrieve phosphatase specific sequences as the main focus of our study was to analyze the phosphatases present in human malaria parasite, P. falciparum. We selected 1322 phosphatase sequences from these model organism proteomes for further analysis. We could identify 67 and 56 phosphatase sequences in P. falciparum based on CDD [29] and PFAM [30] classifications, respectively. Using CDD search, almost similar numbers of phosphatase sequences were identified in other Plasmodium species too. The apicomplexans included in the study have 44 – 71 phosphatases; with the exception of T. gondii, which has 127 candidate phosphatases identified using CDD approach. In comparison to ~250 phosphatases identified in H. sapiens, the number of phosphatases is much lower in Plasmodium species (Figure 1). Amongst the 67 candidate phosphatases identified in Plasmodium genome, only 34 phosphatases have human homologue, whereas six are Plasmodium specific. Human proteins containing phosphatase domain have been classified into six distinct functional and structural groups: protein tyrosine phosphatases (PTPs, 108 members), metal-dependent protein phosphatases (PPMs, 13 members), phosphoprotein phosphatases (PPPs, 15 members), lipid phosphatases (LPs, 37 members), haloacid dehalogenase (HADs, 21 members) and nucleoside-diphosphate-linked moiety X (NUDT, 5 members) [31]. Number and percentage of phosphatases belonging to each group varies among different organisms (Additional file 2). For example, the maximum number of H. sapiens phosphatases belongs to phosphotyrosine phosphatase family, whereas majority of the A. thaliana phosphatases belong to PP2Cc and MPP family.Figure 1


Genome wide in silico analysis of Plasmodium falciparum phosphatome.

Pandey R, Mohmmed A, Pierrot C, Khalife J, Malhotra P, Gupta D - BMC Genomics (2014)

Summary of protein phosphatomes of model organisms selected for the comparative studies.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256932&req=5

Fig1: Summary of protein phosphatomes of model organisms selected for the comparative studies.
Mentions: Using the computational methods described in the Methods section, we collected and screened the predicted proteomes of Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi, Plasmodium cynomolgi, Plasmodium berghei, Plasmodium chabaudi, Eimeria tenella, Toxoplasma gondii, Babesia bovis, Theileria parva, Cryptosporidium parvam, Escherichia coli, Arabidopsis thaliana, Saccharomyces cerevisiae and Homo sapiens for phosphatase sequences. We used text search as well as complete proteome of P. falciparum and for others organisms only text search was performed to retrieve phosphatase specific sequences as the main focus of our study was to analyze the phosphatases present in human malaria parasite, P. falciparum. We selected 1322 phosphatase sequences from these model organism proteomes for further analysis. We could identify 67 and 56 phosphatase sequences in P. falciparum based on CDD [29] and PFAM [30] classifications, respectively. Using CDD search, almost similar numbers of phosphatase sequences were identified in other Plasmodium species too. The apicomplexans included in the study have 44 – 71 phosphatases; with the exception of T. gondii, which has 127 candidate phosphatases identified using CDD approach. In comparison to ~250 phosphatases identified in H. sapiens, the number of phosphatases is much lower in Plasmodium species (Figure 1). Amongst the 67 candidate phosphatases identified in Plasmodium genome, only 34 phosphatases have human homologue, whereas six are Plasmodium specific. Human proteins containing phosphatase domain have been classified into six distinct functional and structural groups: protein tyrosine phosphatases (PTPs, 108 members), metal-dependent protein phosphatases (PPMs, 13 members), phosphoprotein phosphatases (PPPs, 15 members), lipid phosphatases (LPs, 37 members), haloacid dehalogenase (HADs, 21 members) and nucleoside-diphosphate-linked moiety X (NUDT, 5 members) [31]. Number and percentage of phosphatases belonging to each group varies among different organisms (Additional file 2). For example, the maximum number of H. sapiens phosphatases belongs to phosphotyrosine phosphatase family, whereas majority of the A. thaliana phosphatases belong to PP2Cc and MPP family.Figure 1

Bottom Line: Analysis of proteins expression profiles of the 67 phosphatases revealed that 44 phosphatases are expressed in both schizont as well as gametocytes stages.In the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes.Intriguingly, amongst these phosphatases, we could identify six Plasmodium specific phosphatases and 33 putative phosphatases that do not have human orthologs, thereby suggesting that these phosphatases have the potential to be explored as novel antimalarial drug targets.

View Article: PubMed Central - PubMed

Affiliation: Structural and Computational Biology group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. jamal.khalife@pasteur-lille.fr.

ABSTRACT

Background: Eukaryotic cellular machineries are intricately regulated by several molecular mechanisms involving transcriptional control, post-translational control and post-translational modifications of proteins (PTMs). Reversible protein phosphorylation/dephosphorylation process, which involves kinases as well as phosphatases, represents an important regulatory mechanism for diverse pathways and systems in all organisms including human malaria parasite, Plasmodium falciparum. Earlier analysis on P. falciparum protein-phosphatome revealed presence of 34 phosphatases in Plasmodium genome. Recently, we re-analysed P. falciparum phosphatome aimed at identifying parasite specific phosphatases.

Results: Plasmodium database (PlasmoDB 9.2) search, combined with PFAM and CDD searches, revealed 67 candidate phosphatases in P. falciparum. While this number is far less than the number of phosphatases present in Homo sapiens, it is almost the same as in other Plasmodium species. These Plasmodium phosphatase proteins were classified into 13 super families based on NCBI CDD search. Analysis of proteins expression profiles of the 67 phosphatases revealed that 44 phosphatases are expressed in both schizont as well as gametocytes stages. Fourteen phosphatases are common in schizont, ring and trophozoite stages, four phosphatases are restricted to gametocytes, whereas another three restricted to schizont stage. The phylogenetic trees for each of the known phosphatase super families reveal a considerable phylogenetic closeness amongst apicomplexan organisms and a considerable phylogenetic distance with other eukaryotic model organisms included in the study. The GO assignments and predicted interaction partners of the parasite phosphatases indicate its important role in diverse cellular processes.

Conclusion: In the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes. Intriguingly, amongst these phosphatases, we could identify six Plasmodium specific phosphatases and 33 putative phosphatases that do not have human orthologs, thereby suggesting that these phosphatases have the potential to be explored as novel antimalarial drug targets.

Show MeSH
Related in: MedlinePlus