Biochemical properties of purified cathepsin B from Schistosoma mansoni

Ghoneim, Hossam; Klinkert, Mo‐Quen

doi:10.1016/0020-7519(95)00079-8

Cited by 29 publications

(19 citation statements)

References 10 publications

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“…Activated recombinant SmCB1 has very similar biochemical properties to the native parasite enzyme [5]. These include a similar pH optimum with Z-Phe-Arg-AMC as a substrate (pH 5.5-6.0) and similar K m values for Z-PheArg-AMC (wild-type, 21 M; recombinant, 38 M) and Z-Arg-Arg-AMC (wild-type 41 M; recombinant, 46 M).…”

Section: Discussionmentioning

confidence: 67%

See 1 more Smart Citation

Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase

Sajid

McKerrow

Hansell

et al. 2003

Molecular and Biochemical Parasitology

145

142

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Section: Discussionmentioning

confidence: 67%

“…These include cathepsin B1 (SmCB1; a.k.a. Sm31) [4,5], cathepsin L1 [6], cathepsin L2 [7], asparaginyl endopeptidase (SmAE; a.k.a Sm32), or schistosome legumain [8] and cathepsin C [9]. In addition, a schistosome cathepsin D-like aspartic endopeptidase has been described [10].…”

Section: Introductionmentioning

confidence: 99%

Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase

Sajid

McKerrow

Hansell

et al. 2003

Molecular and Biochemical Parasitology

145

142

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“…Hb from ingested or parasitized erythrocytes is their major source of exogenous amino acids for growth, development, and reproduction; the Hb, a ϳ64-kDa tetrameric polypeptide, is comprehensively catabolized by parasite enzymes to free amino acids or small peptides. Intriguingly, all these parasites appear to employ cathepsin D-like aspartic proteases to make initial or early cleavages in the Hb substrate (2)(3)(4).…”

mentioning

confidence: 99%

Hemoglobin-degrading, Aspartic Proteases of Blood-feeding Parasites

Brinkworth¹,

Prociv²,

Loukas³

et al. 2001

Journal of Biological Chemistry

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Blood-feeding parasites, including schistosomes, hookworms, and malaria parasites, employ aspartic proteases to make initial or early cleavages in ingested host hemoglobin. To better understand the substrate affinity of these aspartic proteases, sequences were aligned with and/or three-dimensional, molecular models were constructed of the cathepsin D-like aspartic proteases of schistosomes and hookworms and of plasmepsins of Plasmodium falciparum and Plasmodium vivax, using the structure of human cathepsin D bound to the inhibitor pepstatin as the template. The catalytic subsites S5 through S4 were determined for the modeled parasite proteases. Subsequently, the crystal structure of mouse renin complexed with the nonapeptidyl inhibitor t-butyl-CO-His-Pro-Phe-His-Leu [CHOHCH 2 ]Leu-Tyr-Tyr-Ser-NH 2 (CH-66) was used to build homology models of the hemoglobin-degrading peptidases docked with a series of octapeptide substrates. The modeled octapeptides included representative sites in hemoglobin known to be cleaved by both Schistosoma japonicum cathepsin D and human cathepsin D, as well as sites cleaved by one but not the other of these enzymes. The peptidase-octapeptide substrate models revealed that differences in cleavage sites were generally attributable to the influence of a single amino acid change among the P5 to P4 residues that would either enhance or diminish the enzymatic affinity. The difference in cleavage sites appeared to be more profound than might be expected from sequence differences in the enzymes and hemoglobins. The findings support the notion that selective inhibitors of the hemoglobin-degrading peptidases of blood-feeding parasites at large could be developed as novel anti-parasitic agents.Blood flukes, hookworms, and the malaria parasites are among the most important pathogens of humans in terms of both numbers of people infected and the consequent morbidity and mortality (1). Although phylogenetically unrelated, these parasites all share the same food source; they are obligate blood feeders, or hematophages. Hb from ingested or parasitized erythrocytes is their major source of exogenous amino acids for growth, development, and reproduction; the Hb, a ϳ64-kDa tetrameric polypeptide, is comprehensively catabolized by parasite enzymes to free amino acids or small peptides. Intriguingly, all these parasites appear to employ cathepsin D-like aspartic proteases to make initial or early cleavages in the Hb substrate (2-4).The vertebrate endopeptidase, cathepsin D (EC 3.4.23.5), is a member of the aspartic protease category of hydrolases, which also includes renin, pepsin, chymosin, cathepsin E, HIV 1 protease, and several other enzymes (5, 6). Cathepsin D is expressed in a diverse range of mammalian cells and tissues and is located predominantly in lysosomes (6). The molecule comprises two rather similar lobes, each incorporating a homologous Asp-Thr-Gly catalytic site motif, with the substrate binding groove located between these lobes. In aspartic proteases generally, the nucleophile that attacks...

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“…Protein Sm31 has been identified as the schistosome homologue of human liver cathepsin B (Klinkert et al 1989), and Sm32 was recently identified as a protein with asparaginyl endoproteinase activity (Dalton et al 1996). Over the years, these antigens have been produced by recombinant DNA technology (Davis et al 1987;Klinkert et al 1987;Lipps et al 1996) and in native forms (Chappell & Dresden 1986;Ghoneim & Klinkert 1995) and their suitability as diagnostic antigens for schistosomiasis has been tested in several trials (Ruppel et al , 1990Zerda et al 1987;Idris & Ruppel 1988;Chappell et al 1989Chappell et al , 1990Klinkert et al 1990;1992).…”

Section: Tmih298mentioning

confidence: 99%

“…mansoni Sm31 and Sm32 were purified according to Chappell & Dresden (1986) and Ghoneim & Klinkert (1995). SWAP was subjected to 40᎐70% ammonium sulphate fractionation and the mixture was passed through a gel filtration column containing Ultrogel AcA54.…”

Section: Antigen Preparationsmentioning

confidence: 99%

Diagnostic significance of Schistosoma mansoni proteins Sm31 and Sm32 in human schistosomiasis in an endemic area in Egypt

El-Sayed¹,

Ghoneim²,

Demian³

et al. 1998

Tropical Med Int Health

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SummaryWe performed a series of ELISAs to evaluate the diagnostic significance of two Schistosoma mansoni proteins, Sm31 (cysteine proteinase, cathepsin B) and Sm32 (asparaginyl endopeptidase). Our study populations were chosen from two villages in an endemic area close to Alexandria. Using fusion proteins MS2-Sm31 and MS2-Sm32 as antigens, 70% and 78.9%, respectively, of patient sera from 134 parasitologically confirmed cases reacted positively. The percentage of seropositivity increased to 84.5% when parasite-derived proteins Sm31 and Sm32 were used. The serum levels of antibodies to these two proteins in recombinant or native forms do not correlate with intensity of infection and hence are detected even when egg counts are low, which makes proteins Sm31 and Sm32 useful antigens in the identification of S. mansoni infected cases, particularly in endemic areas in Egypt.keywords Schistosomiasis mansoni, diagnosis, ELISA correspondence Prof.

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Biochemical properties of purified cathepsin B from Schistosoma mansoni

Cited by 29 publications

References 10 publications

Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase

Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase

Hemoglobin-degrading, Aspartic Proteases of Blood-feeding Parasites

Diagnostic significance of Schistosoma mansoni proteins Sm31 and Sm32 in human schistosomiasis in an endemic area in Egypt

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