Ž . Biochimica et Biophysica Acta 1338 1997 156–160 Short sequence-paper Schistosomes express two forms of cathepsin D 1 Joanna Y.M. Wong a,b , Stephen A. Harrop a,b , Sharon R. Day a , Paul J. Brindley a, ) a Molecular Parasitology Unit, Queensland Institute of Medical Research, and Australian Centre for International and Tropical Health and Nutrition, The Bancroft Centre, Post Office, Royal Brisbane Hospital, Herston, Queensland 4029, Australia b Department of Parasitology, The UniÕersity of Queensland, St. Lucia, Queensland 4072, Australia Received 6 November 1996; revised 6 January 1997; accepted 17 January 1997 Abstract We report here a cDNA and its deduced amino acid sequence encoding a cathepsin D-like, aspartic protease expressed by adult stages of the human blood fluke Schistosoma mansoni. The cDNA encodes a short signal peptide, a pro-enzyme peptide of 37 amino acid residues, and a mature enzyme of 377 residues which has strong homology with mammalian cathepsins D. This aspartic protease, although 84% identical in amino acids of the mature enzyme region to the previously reported cathepsin D from the Asian schistosome S. japonicum, differs remarkably from the S. japonicum enzyme in having a carboxyl terminal extension of 43 amino acid residues. These cathepsins D of schistosomes may play pivotal roles in the degradation of hemoglobin obtained by the parasites from ingested host erythrocytes. q 1997 Elsevier Science B.V. All rights reserved. Keywords: Schistosoma mansoni; Aspartic protease; Cathepsin D; Carboxy-terminal extension Schistosomes acquire amino acids necessary for growth and development by metabolizing hemoglobin obtained from ingested host erythrocytes. While the precise biochemical pathways involved have not been determined, several schistosome proteases including cathepsins L, D, B, and C are thought to play key Ž wx. roles in the degradation of hemoglobin see Ref. 1 . If so, these parasite proteases may represent critical targets at which to direct novel, anti-schistosomal Ž Abbreviations: Sjpasp, Schistosoma japonicum Philippine . strain aspartic protease; Smasp, S. mansoni aspartic protease; NH -, amino-; COOH-, carboxyl- 2 ) Corresponding author. Fax: q61 7 33620104. E-mail: paulB@qimr.edu.au 1 The nucleotide sequence reported here was assigned the GenBanke accession no. U60995. Ž wx. therapies see Ref. 1 . Previously we reported the deduced amino acid sequence of a cathepsin D-like, aspartic protease from adult Schistosoma japonicum, showed by Southern hybridization analysis that a gene encoding an homologous enzyme exists in S. mansoni and, furthermore, detected hemoglobin-de- Ž. grading activity ascribable to an aspartic protease s in lysates and excretory-secretory products from S. wx mansoni and S. japonicum 2 . We now report a deduced amino acid sequence of an aspartic protease from S. mansoni which although 84% identical to the S. japonicum cathepsin D-like aspartic protease, dif- fered significantly from it by the presence of a COOH-terminal extension of 43 amino acid residues. An adult S. mansoni cDNA library, constructed in wx the lZap vector as described 3 , was screened by nucleic acid hybridization with the 32 P-labeled cDNA encoding the S. japonicum aspartic protease as the 0167-4838r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0167-4838 97 00019-8