Schistosoma japonicum: Immunoinhibitory Studies on Hemoglobin Digestion Using Heterologous Antiserum to Bovine Cathepsin D

1992 ◽  
Vol 78 (3) ◽  
pp. 454 ◽  
Author(s):  
Burton J. Bogitsh ◽  
Kenneth F. Kirschner ◽  
J. P. Rotmans
Keyword(s):  
Schistosoma Japonicum ◽  
Cathepsin D ◽  
Heterologous Antiserum

Developmental expression of cathepsin D aspartic protease in Schistosoma japonicum

1999 ◽  
Vol 29 (11) ◽  
pp. 1819-1824 ◽  
Author(s):  
Christiana K. Verity ◽  
Donald P. McManus ◽  
Paul J. Brindley
Keyword(s):  
Schistosoma Japonicum ◽  
Cathepsin D ◽  
Aspartic Protease ◽  
Developmental Expression

Homology modeling and SAR analysis of Schistosoma japonicum cathepsin D (SjCD) with statin inhibitors identify a unique active site steric barrier with potential for the design of specific inhibitors

2005 ◽  
Vol 386 (4) ◽  
pp. 339-349 ◽  
Author(s):  
Conor R. Caffrey ◽  
Lenka Placha ◽  
Cyril Barinka ◽  
Martin Hradilek ◽  
Jiří Dostál ◽  
...  
Keyword(s):  
Schistosoma Japonicum ◽  
Active Site ◽  
Cathepsin D ◽  
Three Dimensional ◽  
Homology Model ◽  
Three Dimensional Model ◽  
Pathogenic Yeast ◽  
Active Site Cleft ◽  
Chronic Morbidity ◽  
Sar Analysis

Abstract Proteases that digest the blood-meal of the parasitic fluke Schistosoma are potential targets for therapy of schistosomiasis, a disease of chronic morbidity in humans. We generated a three-dimensional model of the cathepsin D target protease of Schistosoma japonicum (SjCD) utilizing the crystal structure of human cathepsin D (huCD) in complex with pepstatin as template. A homology model was also generated for the related secreted aspartic protease 2 (SAP2) of the pathogenic yeast, Candida albicans. An initial panel of seven statin inhibitors, originally designed for huCD [Majer et al., Protein Sci. 6 (1997), pp. 1458–1466], was tested against the two pathogen proteases. One inhibitor showed poor reactivity with SjCD. Examination of the SjCD active-site cleft revealed that the poor inhibition was due to a unique steric barrier situated between the S2 and S4 subsites. An in silico screen of 20 potential statin scaffolds with the SjCD model and incorporating the steric barrier constraint was performed. Four inhibitors (SJ1–SJ4) were eventually synthesized and tested with SjCD, bovine CD and SAP2. Of these, SJ2 and SJ3 proved moderately more specific for SjCD over bovine CD, with IC50 values of 15 and 60 nM, respectively. The unique steric barrier identified here provides a structural focus for further development of more specific SjCD inhibitors.

Cellular responses to Schistosoma japonicum cathepsin D aspartic protease

2002 ◽  
Vol 24 (7) ◽  
pp. 363-367 ◽  
Author(s):  
Christiana K. Verity ◽  
Donald P. Mcmanus ◽  
Paul J. Brindley
Keyword(s):  
Schistosoma Japonicum ◽  
Cathepsin D ◽  
Cellular Responses ◽  
Aspartic Protease

Vaccine efficacy of recombinant cathepsin D aspartic protease from Schistosoma japonicum

2001 ◽  
Vol 23 (3) ◽  
pp. 153-162 ◽  
Author(s):  
Christiana K. Verity ◽  
Donald P. McManus ◽  
Paul J. Brindley
Keyword(s):  
Schistosoma Japonicum ◽  
Vaccine Efficacy ◽  
Cathepsin D ◽  
Aspartic Protease

Schistosoma japonicum cathepsin D aspartic protease cleaves human IgG and other serum components

Parasitology ◽  
2001 ◽  
Vol 122 (4) ◽  
pp. 415-421 ◽  
Author(s):  
C. K. VERITY ◽  
A. LOUKAS ◽  
D. P. McMANUS ◽  
P. J. BRINDLEY
Keyword(s):  
Schistosoma Japonicum ◽  
Cathepsin D ◽  
Serum Proteins ◽  
Aspartic Protease ◽  
Complement C3 ◽  
Dependent Manner ◽  
Cleavage Sites ◽  
Fab Fragment ◽  
Human Igg ◽  
Amino Terminal

Recombinant cathepsin D aspartic protease of Schistosoma japonicum cleaved human IgG in vitro in a time and dose-dependent manner. Optimal cleavage was seen at pH 3·6–4·5; modest cleavage remained at pH 5·0, and no cleavage was detected above pH 5·0. Amino terminal sequencing of the major cleavage fragments of human IgG identified a Fab fragment from the VH1 domain, and 2 cleavage sites in the CH2 domain below the hinge region. The P1 and P1′ residues at the 2 CH2 cleavage sites were Phe254–Leu255 and Leu325–Thr326, indicating a preference by the schistosome protease for bulky hydrophobic residues flanking the scissile bond. No cleavage of the immunoglobulin light chain was detected. In addition, the recombinant schistosome protease indiscriminately degraded the human serum proteins complement C3 and serum albumin into numerous small fragments. These results demonstrate specific cleavage of human IgG by the recombinant schistosome aspartic protease, and highlight the broad range digestive specificity of the enzyme which may play a role in the degradation of host serum proteins ingested as part of the schistosome bloodmeal.

Ultrastructure of Cercarial Tails

1974 ◽  
Vol 32 ◽  
pp. 180-181
Author(s):  
Richard S. Demaree ◽  
Donald M. Wootton
Keyword(s):  
Schistosoma Japonicum ◽  
Intermediate Hosts ◽  
Suitable Host ◽  
Ultrastructural Studies ◽  
Tail Structure

Cercariae (juvenile trematodes with tails) emerge from mollusk intermediate hosts and swim toward definitive hosts or encystment objects. The locomotor power is furnished by the tail. Upon reaching a suitable host or encystment object, the tail is cast off and the cercariae penetrate and/or encyst. Ultrastructural studies of cercariae are sparse. There is even lessUltrastructural studies of cercariae are sparse. There is even less information about the tail structure; and body-to-tail morphology has been documented only for Acanthatrium oregonense and Schistosoma japonicum.

644: Cathepsin D is a Marker for Early Stage Renal Cell Cancer and Predicts the Presence of Distant Metastases

2005 ◽  
Vol 173 (4S) ◽  
pp. 175-175
Author(s):  
Axel S. Merseburger ◽  
Joerg Hennenlotter ◽  
Perikles Simon ◽  
Marcus Horstmann ◽  
Arnulf Stenzl ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cathepsin D ◽  
Early Stage ◽  
Cell Cancer ◽  
Distant Metastases

Physiological Effects of Nonimmune Platelet Associated Immunoglobulin G

1981 ◽  
Vol 45 (01) ◽  
pp. 027-033 ◽  
Author(s):  
K Sugiura ◽  
M Steiner ◽  
M Baldini
Keyword(s):  
Shape Change ◽  
Fluorescein Isothiocyanate ◽  
Recovery Phase ◽  
Human Platelets ◽  
Serotonin Release ◽  
Platelet Volume ◽  
Igg Antibody ◽  
Heterologous Antiserum ◽  
Igg Binding ◽  
Series Of Experiments

SummaryThe function of nonimmune IgG associated with platelets is unknown. In a series of experiments we have investigated this problem, relating amount of platelet-associated IgG (PAIgG) to platelet volume, serotonin release, adherence of platelets to monocytes and platelet senescence. Most of these studies were performed with human platelets. Platelets freed of preexisting PAIgG by incubation at 22° C were incubated with IgG in a series of concentrations ranging from 0.4 — 27.0 X10-6 M. The IgG preparations used were demonstrably free of aggregated forms of the protein. The amount of PAIgG bound to platelets was determined by the use of fluorescein isothiocyanate-conjugated anti-IgG antibody (F-anti-IgG antibody) which was quantified in a fluorospectrophotometer. Newly bound IgG was assayed similarly by the use of F-IgG. A dose-dependent increase in platelet volume was associated with the binding of nonimmune IgG by platelets. The process which leveled off at an IgG concentration of 1.2 —1.5 X10-5 M was almost fully reversible and was not due to platelet shape change or aggregation. Release of serotonin from IgG-treated platelets was relatively small but to the extent that it occurred was positively related to the IgG concentration to which platelets were exposed. Adherence to autologous monocytes studied quantitatively by the use of formaldehyde-fixed cells was also positively related to the amount of IgG on the platelets. Normal or IgG-defident serum had a potent inhibitory (noncompetitive) action on the binding of F-IgG and F-anti-human IgG antibody to human platelets. Cohorts of platelets prepared in rabbits during the recovery phase of immunological thrombocytopenia induced by injection of heterologous antiserum, showed an age-dependent increase of PAIgG and of IgG binding. These results suggest that PAIgG plays a role in the clearance of senescent platelets.

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