title: The protein-phosphatome of the human malaria parasite Plasmodium falciparum.
abstract: BACKGROUND
  Malaria, caused by the parasitic protist Plasmodium falciparum, represents a major public health problem in the developing world. The P. falciparum genome has been sequenced, which provides new opportunities for the identification of novel drug targets. We report an exhaustive analysis of the P. falciparum genomic database (PlasmoDB) aimed at identifying and classifying all protein phosphatases (PP) in this organism.
  
  
  RESULTS
  Using a variety of bioinformatics tools, we identified 27 malarial putative PP sequences within the four major established PP families, plus 7 sequences that we predict to dephosphorylate "non-protein" substrates. We constructed phylogenetic trees to position these sequences relative to PPs from other organisms representing all major eukaryotic phyla except Cercozoans (for which no full genome sequence is available). Predominant observations were: (i) P. falciparum possessed the smallest phosphatome of any of the organisms investigated in this study; (ii) no malarial PP clustered with the tyrosine-specific subfamily of the PTP group (iii) a cluster of 7 closely related members of the PPM/PP2C family is present, and (iv) some P. falciparum protein phosphatases are present in clades lacking any human homologue.
  
  
  CONCLUSIONS
  The considerable phylogenetic distance between Apicomplexa and other Eukaryotes is reflected by profound divergences between the phosphatome of malaria parasites and those of representative organisms from all major eukaryotic phyla, which might be exploited in the context of efforts for the discovery of novel targets for antimalarial chemotherapy.
authors.affiliation: INSERM U609, Wellcome Centre for Molecular Parasitology, University of Glasgow, Glasgow, Scotland, UK. jw149j@udcf.gla.ac.uk
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wilkes
authors.forename: Christian
authors.initials: C
authors.lastname: Doerig
mesh_terms: D000818:Animals; D023281:Genomics; D006801:Humans; D008390:Markov Chains; D010749:Phosphoprotein Phosphatases / Q000302:isolation & purification*; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics*
chemical_list: D010749:Phosphoprotein Phosphatases
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17314-9
references.pmid: 16301539
references.citation: Genes Dev. 2004 Feb 15;18(4):448-60
references.pmid: 14977918
references.citation: Proteins. 2007 Sep 1;68(4):893-914
references.pmid: 17557329
references.citation: Int J Parasitol. 2002 Dec 4;32(13):1575-85
references.pmid: 12435442
references.citation: Mol Cancer Ther. 2005 Nov;4(11):1653-61
references.pmid: 16275986
references.citation: Biochim Biophys Acta. 2002 Sep 13;1577(2):261-275
references.pmid: 12213657
references.citation: BMC Genomics. 2005 Mar 07;6:30
references.pmid: 15752424
references.citation: Curr Opin Cell Biol. 2005 Apr;17(2):197-202
references.pmid: 15780597
references.citation: Science. 2003 Oct 24;302(5645):639-42
references.pmid: 14576433
references.citation: Mol Microbiol. 2001 Feb;39(4):973-81
references.pmid: 11251817
references.citation: Trends Cell Biol. 2000 Jan;10(1):17-24
references.pmid: 10603472
references.citation: Curr Issues Mol Biol. 2005 Jan;7(1):57-79
references.pmid: 15580780
references.citation: Mol Biochem Parasitol. 1998 Sep 15;95(2):287-95
references.pmid: 9803420
references.citation: Mol Biol Evol. 2001 Mar;18(3):448-52
references.pmid: 11230548
references.citation: Mol Biochem Parasitol. 2008 Mar;158(1):1-10
references.pmid: 18096253
references.citation: Cell Mol Life Sci. 2002 Jun;59(6):941-9
references.pmid: 12169024
references.citation: Biochem J. 1995 Oct 1;311 ( Pt 1):17-29
references.pmid: 7575450
references.citation: Nat Protoc. 2007;2(4):953-71
references.pmid: 17446895
references.citation: Trends Biochem Sci. 1996 Nov;21(11):413-7
references.pmid: 8987394
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):276-80
references.pmid: 11752314
references.citation: J Bacteriol. 2005 May;187(10):3511-20
references.pmid: 15866939
references.citation: Mol Biochem Parasitol. 2001 Jun;115(1):29-39
references.pmid: 11377737
references.citation: Expert Opin Ther Targets. 2007 Mar;11(3):279-90
references.pmid: 17298288
references.citation: Biochemistry. 2007 Mar 27;46(12):3595-604
references.pmid: 17328562
references.citation: Science. 2003 Sep 12;301(5639):1503-8
references.pmid: 12893887
references.citation: Mol Microbiol. 2000 Mar;35(5):1005-16
references.pmid: 10712683
references.citation: Traffic. 2005 Dec;6(12):1063-9
references.pmid: 16262718
references.citation: Mol Biochem Parasitol. 1999 Apr 30;99(2):167-81
references.pmid: 10340482
references.citation: J Mol Biol. 2000 Sep 8;302(1):205-17
references.pmid: 10964570
references.citation: Curr Med Chem. 2005;12(1):1-22
references.pmid: 15638728
references.citation: J Biol Chem. 1999 Oct 15;274(42):29912-20
references.pmid: 10514473
references.citation: Biochemistry. 1995 Feb 14;34(6):1988-96
references.pmid: 7531497
references.citation: Mol Biol Evol. 2006 Feb;23(2):254-67
references.pmid: 16221896
references.citation: Genome Biol. 2003;4(5):111
references.pmid: 12734000
references.citation: FEBS Lett. 2005 Jun 13;579(15):3278-86
references.pmid: 15913612
references.citation: Future Microbiol. 2006 Jun;1(1):127-41
references.pmid: 17661691
references.citation: Mol Biochem Parasitol. 2003 Feb;126(2):239-50
references.pmid: 12615323
references.citation: Curr Opin Cell Biol. 2006 Dec;18(6):623-31
references.pmid: 17030123
references.citation: J Biol Chem. 1998 May 1;273(18):11241-7
references.pmid: 9556615
references.citation: Methods Mol Biol. 2007;365:287-98
references.pmid: 17200569
references.citation: Eur J Biochem. 1994 Feb 15;220(1):225-37
references.pmid: 8119291
references.citation: BMC Genomics. 2004 Oct 12;5:79
references.pmid: 15479470
references.citation: FEBS Lett. 1990 Nov 26;275(1-2):44-8
references.pmid: 2175718
references.citation: Trends Biochem Sci. 1997 Jul;22(7):245-51
references.pmid: 9255065
references.citation: Science. 2004 Dec 10;306(5703):1934-7
references.pmid: 15591203
references.citation: BMC Evol Biol. 2004 Nov 19;4:47
references.pmid: 15555063
references.citation: Nature. 2002 Oct 3;419(6906):498-511
references.pmid: 12368864
references.citation: J Cell Sci. 1996 Dec;109 ( Pt 12):2865-74
references.pmid: 9013334
references.citation: EMBO J. 1996 Dec 16;15(24):6798-809
references.pmid: 9003755
references.citation: Oncogene. 2007 May 14;26(22):3203-13
references.pmid: 17496916
references.citation: BMC Genomics. 2005 Sep 15;6:127
references.pmid: 16164760
references.citation: Int J Parasitol. 2002 Jun;32(6):739-47
references.pmid: 12062492
references.citation: Trends Parasitol. 2006 Dec;22(12):543-6
references.pmid: 17029963
references.citation: Proteins. 2005 Jan 1;58(1):180-9
references.pmid: 15515182
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D247-51
references.pmid: 16381856
references.citation: Clin Transl Oncol. 2006 Mar;8(3):153-60
references.pmid: 16648114
references.citation: Bioinformatics. 1998;14(9):755-63
references.pmid: 9918945
references.citation: J Mol Biol. 2007 Dec 7;374(4):899-909
references.pmid: 17976645
references.citation: Mol Biochem Parasitol. 2002 Apr 9;120(2):257-68
references.pmid: 11897131
references.citation: Science. 2003 Jun 13;300(5626):1703-6
references.pmid: 12805537
references.citation: Mol Biochem Parasitol. 2004 Feb;133(2):297-310
references.pmid: 14698441
references.citation: Cell Signal. 2002 Sep;14(9):745-50
references.pmid: 12034355
references.citation: Annu Rev Biophys Biomol Struct. 1998;27:133-64
references.pmid: 9646865
references.citation: J Exp Bot. 2007;58(13):3503-11
references.pmid: 17951602
references.citation: Malar J. 2002 Apr 26;1:5
references.pmid: 12057017
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Biochim Biophys Acta. 2005 Dec 30;1754(1-2):291-5
references.pmid: 16194631
references.citation: J Biol Chem. 2003 Apr 18;278(16):13627-32
references.pmid: 12556522
references.citation: BMC Genomics. 2007 Nov 26;8:434
references.pmid: 18039372
references.citation: Trends Biochem Sci. 2001 Jun;26(6):369-76
references.pmid: 11406410
references.citation: Nucleic Acids Res. 2002 Apr 1;30(7):1575-84
references.pmid: 11917018
references.citation: BMC Microbiol. 2001;1:31
references.pmid: 11737864
references.citation: Eur J Biochem. 1997 Oct 1;249(1):98-106
references.pmid: 9363759
references.citation: BMC Mol Biol. 2004 Jul 01;5:6
references.pmid: 15230980
references.citation: Trends Biochem Sci. 2001 Jul;26(7):426-31
references.pmid: 11440854
references.citation: J Biol Chem. 2003 Jul 11;278(28):26078-85
references.pmid: 12721286
references.citation: Trends Plant Sci. 2004 May;9(5):236-43
references.pmid: 15130549
references.citation: Curr Cancer Drug Targets. 2006 Sep;6(6):519-32
references.pmid: 17017875
references.citation: Curr Opin Cell Biol. 2006 Apr;18(2):185-91
references.pmid: 16488126
references.citation: Mol Microbiol. 2005 Jan;55(1):184-96
references.pmid: 15612927
references.citation: Adv Pharmacol. 1996;36:67-89
references.pmid: 8783555
references.citation: Science. 2004 Dec 10;306(5703):1930-3
references.pmid: 15591202
references.citation: Int J Parasitol. 2008 Sep;38(11):1279-95
references.pmid: 18547579
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Methods Enzymol. 1991;200:38-62
references.pmid: 1956325
references.citation: Methods Mol Biol. 2007;365:335-46
references.pmid: 17200573
references.citation: Science. 2003 Jan 31;299(5607):705-8
references.pmid: 12560551