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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.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.In the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes.

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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P. falciparumphosphatase domain classification on the basis of PFAM and CDD.
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Fig3: P. falciparumphosphatase domain classification on the basis of PFAM and CDD.

Mentions: Based on the classification adapted for human phosphatases and considering the other functional phosphatase domain, we grouped Plasmodium phosphatases into 13 super families using CDD. Schematic diagram of phosphatases in each superfamily is shown in Figure 2 (Additional file 3). Conserved domain alignment of P. falciparum phosphatases are shown in Additional files 4 and 5. Table 1 shows the name, accession number and classes of Plasmodium phosphatases analysed in the present study. Identity and the number of phosphatases observed in each family remained proportionally similar in the CDD or PFAM domain classifications (Figure 3). The protein family assignment of the phosphatases revealed interesting patterns due to the reason that we used a broader selection criterion as compared to previous studies, enabling identification of complete spectrum of phosphatases. The phosphatase family with highest number of Plasmodium phosphatases is the MPP family with 18 phosphatases, whereas few families such as PTPLA (Protein tyrosine phosphatase-like protein) and CYTH-like_Pase (Triphosphate Tunnel Metaloenzyme Phosphatase) have only single member. Several sequences analysed in the study have more than one conserved phosphatase domain, for example PF3D7_1466100 has MPP as well as Kelch like superfamily domain. Kelch family of phosphatases are present in A. thaliana and in other plants. Major expansion of protein phosphatase type with MPP and PP2Cc superfamily in P. falciparum was similar to that observed in A. thaliana. In H. sapiens, PTP superfamily is the largest group in contrast to other model organism studied here. These genome specific expansions probably reflect the evolutionary pressure for a flexible and complex intracellular signalling in these multicellular organisms, most likely acquired and developed during the course of evolution.Figure 2


Genome wide in silico analysis of Plasmodium falciparum phosphatome.

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

P. falciparumphosphatase domain classification on the basis of PFAM and CDD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: P. falciparumphosphatase domain classification on the basis of PFAM and CDD.
Mentions: Based on the classification adapted for human phosphatases and considering the other functional phosphatase domain, we grouped Plasmodium phosphatases into 13 super families using CDD. Schematic diagram of phosphatases in each superfamily is shown in Figure 2 (Additional file 3). Conserved domain alignment of P. falciparum phosphatases are shown in Additional files 4 and 5. Table 1 shows the name, accession number and classes of Plasmodium phosphatases analysed in the present study. Identity and the number of phosphatases observed in each family remained proportionally similar in the CDD or PFAM domain classifications (Figure 3). The protein family assignment of the phosphatases revealed interesting patterns due to the reason that we used a broader selection criterion as compared to previous studies, enabling identification of complete spectrum of phosphatases. The phosphatase family with highest number of Plasmodium phosphatases is the MPP family with 18 phosphatases, whereas few families such as PTPLA (Protein tyrosine phosphatase-like protein) and CYTH-like_Pase (Triphosphate Tunnel Metaloenzyme Phosphatase) have only single member. Several sequences analysed in the study have more than one conserved phosphatase domain, for example PF3D7_1466100 has MPP as well as Kelch like superfamily domain. Kelch family of phosphatases are present in A. thaliana and in other plants. Major expansion of protein phosphatase type with MPP and PP2Cc superfamily in P. falciparum was similar to that observed in A. thaliana. In H. sapiens, PTP superfamily is the largest group in contrast to other model organism studied here. These genome specific expansions probably reflect the evolutionary pressure for a flexible and complex intracellular signalling in these multicellular organisms, most likely acquired and developed during the course of evolution.Figure 2

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.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.In the study presented here, we reviewed the P. falciparum phosphatome to show presence of 67 candidate phosphatases in P. falciparum genomes/proteomes.

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