Phosphatidylinositol-and related-kinases: a genome-wide survey of classes and subtypes in the Schistosoma mansoni genome for designing subtype-specific inhibitors.
Phosphatidylinositol kinases (PIK) are at the heart of one of the major pathways of intracellular signal transduction. The signals made by PIK influence a wide variety of cellular functions, including cell growth, differentiation and survival, glucose metabolism and cytoskeletal organization. Wortmannin strongly binds in vitro to all PIK subtypes and it is therefore an effective antiproliferative agent. This study is the first report on a survey made by similarity searches against Schistosoma mansoni genome available to date for phosphatidylinositol- and related-kinases (SmPIKs). We classified the SmPIKs according to five models (1-5). SmPIK sequences were retrieved from GeneDB (http://www.genedb.org) by means of a combinatorial approach which uses terms defined in genome annotation associated with PFAM (Protein Families) domains, BLAST analysis and COGs (Clusters of Orthologous Groups of proteins). This approach detects the kinase (catalytic) domain structure and also the recently described FAT and FATC motifs.
Bahia
Diana
D
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, UNIFESP, Rua Botucatu 862, 6o andar, 04023-062 São Paulo, SP, Brazil. dianabahia@hotmail.com
Oliveira
Luciana Márcia
LM
Mortara
Renato Arruda
RA
Ruiz
Jerônimo Conceição
JC
D000595:Amino Acid Sequence; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry* / Q000494:pharmacology; D019295:Computational Biology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D049751:Genome, Helminth; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000145:classification* / Q000235:genetics; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010802:Phylogeny; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000235:genetics; D017422:Sequence Analysis, DNA
D000871:Anthelmintics; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors