title: Genome wide in silico analysis of Plasmodium falciparum phosphatome.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Rajan
authors.initials: R
authors.lastname: Pandey
authors.forename: Asif
authors.initials: A
authors.lastname: Mohmmed
authors.forename: Christine
authors.initials: C
authors.lastname: Pierrot
authors.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.
authors.forename: Jamal
authors.initials: J
authors.lastname: Khalife
authors.forename: Pawan
authors.initials: P
authors.lastname: Malhotra
authors.forename: Dinesh
authors.initials: D
authors.lastname: Gupta
mesh_terms: D019295:Computational Biology; D030541:Databases, Genetic; D055106:Genome-Wide Association Study; D023281:Genomics; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008018:Life Cycle Stages / Q000235:genetics; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D040901:Proteomics; D015800:Protozoan Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D010744:Phosphoric Monoester Hydrolases