Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite.
The search for novel antimalarial drug targets is urgent due to the growing resistance of Plasmodium falciparum parasites to available drugs. Proteases are attractive antimalarial targets because of their indispensable roles in parasite infection and development, especially in the processes of host erythrocyte rupture/invasion and hemoglobin degradation. However, to date, only a small number of proteases have been identified and characterized in Plasmodium species. Using an extensive sequence similarity search, we have identified 92 putative proteases in the P. falciparum genome. A set of putative proteases including calpain, metacaspase, and signal peptidase I have been implicated to be central mediators for essential parasitic activity and distantly related to the vertebrate host. Moreover, of the 92, at least 88 have been demonstrated to code for gene products at the transcriptional levels, based upon the microarray and RT-PCR results, and the publicly available microarray and proteomics data. The present study represents an initial effort to identify a set of expressed, active, and essential proteases as targets for inhibitor-based drug design.
Wu
Yimin
Y
Department of Protistology, American Type Culture Collection, Manassas, Virginia 20110, USA.
Wang
Xiangyun
X
Liu
Xia
X
Wang
Yufeng
Y
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002154:Calpain / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling / Q000379:methods; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D018503:Genome, Protozoan; D006801:Humans; D016778:Malaria, Falciparum / Q000201:enzymology* / Q000469:parasitology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D011237:Predictive Value of Tests; D016415:Sequence Alignment / Q000379:methods; D012697:Serine Endopeptidases / Q000235:genetics
D008565:Membrane Proteins; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase; D002154:Calpain