CA/C1 peptidases of the malaria parasites Plasmodium falciparum and P. berghei and their mammalian hosts--a bioinformatical analysis.
In genome-wide screens we studied CA/C1 peptidases of malaria-causing plasmodia and their hosts (man and mouse). For Plasmodium falciparum and P. berghei, several new CA/C1 peptidase genes encoding proteases of the L- and B-family with specific promoter modules were identified. In addition, two new human CA/C1 peptidase loci and one new mouse gene locus were found; otherwise, the sets of CA/C1 peptidase genes in man and mouse seem to be complete now. In each species studied there is a multitude of CA/C1 peptidases with lysosomal localization signals and partial functional overlap according to similar but subfamily-specific structures. Individual target structures in plasmodia include residues specifically different in CA/C1 peptidase subsite 2. This is of medical interest considering CA/C1 peptidase inhibition for chemotherapy in malaria, malignancies and other diseases. Promoter structures and mRNA regulation differ widely among CA/C1 peptidase subfamilies and between mammals and plasmodia. We characterized promoter modules conserved in mouse and man for the CA/C1 peptidase families B and L (with the L-like subfamily, F-like subfamily and mouse-specific J-like subfamily). RNA motif searches revealed conserved regulatory elements such as GAIT elements; plasmodial CA/C1 peptidase mRNA elements include ARE elements and mammalian mRNAs contain 15-lox DICE elements.
Xiao
Ke
K
Lehrstuhl für Bioinformatik, Universität Würzburg, Biozentrum, D-97074 Würzburg, Germany.
Jehle
Franz
F
Peters
Christoph
C
Reinheckel
Thomas
T
Schirmer
R Heiner
RH
Dandekar
Thomas
T
D000818:Animals; D019295:Computational Biology; D015971:Gene Expression Regulation, Enzymologic; D056426:Genetic Loci; D006801:Humans; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D010962:Plasmodium berghei / Q000201:enzymology*; D010963:Plasmodium falciparum / Q000201:enzymology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional
D012333:RNA, Messenger; D010447:Peptide Hydrolases