Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity.
Schistosome helminths constitute a major health risk for the human population in many tropical areas. We demonstrate for the first time that several developmental stages of the human parasite Schistosoma mansoni express arginase, which is responsible for the hydrolysis of l-arginine to l-ornithine and urea. Arginase activity by alternatively activated macrophages is an essential component of the mammalian host response in schistosomiasis. However, it has not been previously shown that the parasite also expresses arginase when it is in contact with the mammalian host. After cloning and sequencing the cDNA encoding the parasite enzyme, we found that many structural features of human arginase are well conserved in the parasite ortholog. Subsequently, we discovered that S. mansoni arginase shares many similar molecular, biochemical and functional properties with both human arginase isoforms. Nevertheless, our data also reveal striking differences between human and schistosome arginase. Particularly, we found evidence that schistosome arginase activity depends upon disulphide bonds by cysteines, in contrast to human arginase. In conclusion, we report that S. mansoni arginase is well adapted to the physiological conditions that exist in the human host.
Fitzpatrick
Jennifer M
JM
Department of Pathology, University of Cambridge, UK.
Fuentes
Jose M
JM
Chalmers
Iain W
IW
Wynn
Thomas A
TA
Modolell
Manuel
M
Hoffmann
Karl F
KF
Hesse
Matthias
M
D000595:Amino Acid Sequence; D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D001700:Biomphalaria / Q000469:parasitology; D003001:Cloning, Molecular; D018509:DNA, Helminth / Q000032:analysis / Q000235:genetics; D004220:Disulfides / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006790:Host-Parasite Interactions; D006801:Humans; D008018:Life Cycle Stages; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D012550:Schistosoma mansoni / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D012555:Schistosomiasis mansoni / Q000201:enzymology* / Q000469:parasitology; D016415:Sequence Alignment; D040681:Structural Homology, Protein
D018509:DNA, Helminth; D004220:Disulfides; D001119:Arginase