Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MUC1 is a mucin-type glycoprotein that is integrally disposed in the apical plasma membrane of the lactating epithelial cell and protrudes from the cell surface into the alveolar lumen where milk is stored. Envelopment of milk fat globules by this membrane accomplishes their secretion and conveys MUC1 into milk. The human form of this mucin has been detected in many other organs, tissues and body fluids. It projects from the cell surface as long filaments. In the human and a number of other species, MUC1 is polymorphic due to variable numbers of a tandemly repeated segment 20 amino acids in length. The individual codominantly expresses two alleles for the mucin so that differences in its size among individuals and between the two forms of an individual are observed. The tandem repeats are rich in serines and threonines which serve as O-glycosylation sites. Carbohydrate content of MUC1, as isolated from milk of human, bovine and guinea pig, is approximately 50%. The oligosaccharides carry substantial sialic acid at their termini and this accounts for two putative functions of this mucin, i.e., to keep ducts and lumens open by creating a strong negative charge on the surface of epithelial cells which would repel opposite sides of a vessel, and to bind certain pathogenic microorganisms. MUC1 is protease resistant (trypsin, chymotrypsin and pepsin) and large fragments of it can be found in the feces of some but not all breast-fed infants. MUC1 has a highly varied structure because of its polymorphism, qualitative and quantitative variations in its glycosylation between tissues, individuals and species, and differences due to divergence in the nucleotide sequences among species. Sequencing of the MUC1 gene for various species is showing promise of revealing unique evolutionary relationships and has already indicated conserved aspects of the molecule that may be functionally important. Among these are positions of serine, threonine and proline in the tandem repeats and a high degree of homology in the transmembrane and cytoplasmic segments of the molecule.
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PMID:The epithelial mucin, MUC1, of milk, mammary gland and other tissues. 854 3

The tumour-associated epitope recognised by monoclonal antibody (MAb) 4D3 is expressed on a high m.w. mucin glycoprotein preparation known as small intestinal mucin antigen (SIMA). This epitope is detected in tissue from a high proportion of patients with colorectal cancer, and elevated levels occur in serum from a significant number of such patients, highlighting the potential clinical utility of MAb 4D3. In the present study, insight into the composition and structure of the carbohydrate epitope recognised by MAb 4D3 was gained following characterisation of 2 glycopeptides that co-purified with SIMA. Sequence analysis of 1 of these glycopeptides revealed that it was identical to the glycoprotein alpha-1-anti-chymotrypsin. This glycoprotein was subsequently deglycosylated to yield 5 forms corresponding to alpha-1-anti-chymotrypsin substituted with 4, 3, 2, 1 or no branched glycans. MAb 4D3 was reactive with each of the glycosylated forms, including the form carrying only 1 branched glycan, but did not react with fully deglycosylated alpha-1-anti-chymotrypsin. MAb 4D3 also reacted to different extents with ovine, bovine or porcine submaxillary mucins, each of which has a different amount of the O-linked sialylated disaccharide known as sialosyl Tn. Of these mucins, MAb 4D3 was most reactive with ovine submaxillary mucin, in which almost all of the carbohydrate chains are sialosyl Tn. Reactivity of MAb 4D3 towards isolated glycans, sialosyl Tn and related structures led to the conclusion that the preferred MAb 4D3 epitope involves the sialylated N-acetyl galactosamine disaccharide as well as an additional monosaccharide present on a neighbouring carbohydrate chain. Although the preferred epitope recognised by MAb 4D3 involves this sialylated disaccharide, the specificity of MAb 4D3 was different from that of other MAbs with a reported specificity for sialosyl Tn.
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PMID:Characterisation of the tumour-associated carbohydrate epitope recognised by monoclonal antibody 4D3. 864 26

Three monoclonal antibodies (mAbs), M344, M300 and M75, were shown to define a unique tumour-associated antigen (TAA) of superficial bladder tumours. The antigenic determinants are expressed on a very-high-molecular-mass component and, in about 50% of the positive samples, one determinant is also detected on a 62 kDa molecular species, observed only under reducing conditions. The objectives of the present study were to characterize further this TAA by analysing (1) the biochemical nature of the epitopes recognized by the three mAbs, and (2) the biochemical and structural features of the molecule bearing them. The antigenicity was resistant to heat denaturation, trypsin and alpha-chymotrypsin treatments but highly sensitive to papain and Pronase digestion. NaIO4 oxidation decreased reactivity to mAbs M344 and M300 but enhanced reactivity to mAb M75. The three determinants were insensitive to beta-galactosidase and alpha-L-fucosidase but were sensitive to Vibrio cholerae neuraminidase. None of the three mAbs reacted with ovine, bovine or porcine submaxillary mucins. Deglycosylation with O-glycosidase or trifluoromethanesulphonic acid completely abolished the reactivity of the mAbs whereas N-glycosidase F deglycosylation had no appreciable effect. The presence on the molecule of cryptic Gal(beta(1-3))GalNAc as a major core disaccharide was demonstrated by a heterologous sandwich assay using mAb M75 and peanut agglutinin. Thiol reduction using beta-mercaptoethanol increased mobility of the high-molecular-mass component in polyacrylamide gels. We thus conclude that mAbs M344 and M300 react with sialylated carbohydrate epitopes, and mAb M75 reacts with a partially cryptic and periodate-resistant sialylated epitope expressed on a typical secreted high-molecular-mass oligomeric mucin which we named MAUB for mucin antigen of the urinary bladder.
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PMID:Biochemical analysis of a bladder-cancer-associated mucin: structural features and epitope characterization. 903 80

The abilities of isolates of saprophytes (Neurospora crassa, Aspergillus nidulans), an opportunistic human pathogen (Aspergillus fumigatus), an opportunistic insect pathogen (Aspergillus flavus), plant pathogens (Verticillium albo-atrum, Verticillium dahliae, Nectria haematococca), a mushroom pathogen (Verticillium fungicola) and entomopathogens (Verticillium lecanii, Beauveria bassiana, Metarhizium anisopliae) to utilize plant cell walls and insect cuticle components in different nutrient media were compared. The pathogens showed enzymic adaptation to the polymers present in the integuments of their particular hosts. Thus, the plant pathogens produced high levels of enzymes capable of degrading pectic polysaccharides, cellulose and xylan, as well as cutinase substrate, but secreted little or no chitinase and showed no proteolytic activity against elastin and mucin. The entomopathogens and V. fungicola degraded a broad spectrum of proteins (including elastin and mucin) but, except for chitinase, cellulase (V. lecanii and V. fungicola only) and cutinase (B. bassiana only), produced very low levels of polysaccharidases. The saprophytes (Neu. crassa and A. nidulans) and the opportunistic pathogens (A. fumigatus and A. flavus) produced the broadest spectrum of protein and polysaccharide degrading enzymes, indicative of their less specialized nutritional status. V. lecanii and V. albo-atrum were compared in more detail to identity factors that distinguish plant and insect pathogens. V. albo-atrum, but not V. lecanii, grew well on different plant cell wall components. The major class of proteases produced in different media by isolates of V. albo-atrum and V. dahliae were broad spectrum basic (pI > 10) trypsins which degrade Z-AA-AA-Arg-NA substrates (Z, benzoyl; AA, various amino acids; Na, nitroanilide), hide protein azure and insect (Manduca sexta) cuticles. Analogous peptidases were produced by isolates of V. lecanii and V. fungicola but they were specific for Z-Phe-Val-Arg-NA. V. albo-atrum and V. dahliae also produced low levels of neutral (pI ca 7) and basic (pI ca 9.5) subtilisin-like proteases active against a chymotrypsin substrate (Succinyl-Ala2-Pro-Phe-NA) and insect cuticle. In contrast, subtilisins comprised the major protease component secreted by V. lecanii and V. fungicola. Both V. lecanii and V. albo-atrum produced the highest levels of subtilisin and trypsin-like activities during growth on collagen or insect cuticle. Results are discussed in terms of the adaptation of fungi to the requirements of their ecological niches.
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PMID:Adaptation of proteases and carbohydrates of saprophytic, phytopathogenic and entomopathogenic fungi to the requirements of their ecological niches. 920 74

Although clusters of pancreatic acinar cells (CPACs) have been reported in gastric mucosa of adults, they have not been described in children. We reviewed 283 pediatric gastric (239 antral and 44 corpus) mucosal biopsies during a 2-year period and detected CPACs in 10 antral biopsy samples. These biopsy samples were stained immunohistochemically for pancreatic exocrine markers (trypsin, chymotrypsin, alpha-amylase, and lipase) and a panel of regulatory substances (insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin, and serotonin). Double immunostaining for colocalization of chromogranins and trypsin as well as mucin and trypsin also were performed on all cases. CPACs were seen in antral mucosa in a background of either normal or minimally inflamed mucosa, without any atrophy or metaplasia, and were positive for all pancreatic exocrine markers. Stray chromogranin-positive cells in the CPACs were also immunopositive for somatostatin, gastrin, or serotonin. All CPACs showed a few hybrid (amphicrine) cells that coexpressed both chromogranin and trypsin. In one case, ultrastructural examination showed such cells to contain both zymogen and neurosecretory granules. Although the presence of CPACs exclusively in the antrum is most likely the result of a sampling bias, the presence of hybrid cells with an amphicrine phenotype suggests that CPACs probably result from an aberration of stem cell differentiation.
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PMID:Pancreatic acinar cell clusters in pediatric gastric mucosa. 942 22

Ovarian cyst fluid has been a valuable source of the mucins (traditionally termed "blood group substances") that were used for the elucidation of the structures of the ABO Lewis blood group determinants, but the identity of the mucin peptide core(s) carrying these carbohydrate specificities is not known. An ovarian cyst fluid mucin was purified, deglycosylated with HF and digested with trypsin or chymotrypsin to yield a number of peptides. Amino acid sequencing of these peptides yielded five different sequences which showed complete or partial homology to the MUC-6 apomucin deduced from DNA sequencing. As no other sequences were identified, it is concluded that MUC-6 is the major mucin core structure of ovarian cyst fluid mucin.
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PMID:MUC-6 mucin is a major component of "blood group substance" from human ovarian cyst fluid. 1077 94

To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.
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PMID:Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. 1177 Jul 1

Peritrophic membrane (PM) proteins are important determinants for the structural formation and function of the PM. We identified two new chitin binding proteins, named CBP1 and CBP2, from the PM of Trichoplusia ni larvae by cDNA cloning. The proteins contain 12 and 10 tandem chitin binding domains in CBP1 and CBP2, respectively. Chitin binding studies demonstrated the chitin binding activity of CBP1 and CBP2, and confirmed the chitin binding domain sequence predicted by sequence analysis. Both CBP1 and CBP2 were not mucin-like glycoproteins, however, they were highly resistant to proteolytic degradation by trypsin. We found that in CBP1 and CBP2, potential trypsin and chymotrypsin cleavage sites reside primarily within the chitin binding domain sequences, limiting exposure of the potential cleavage sites to the digestive proteinases. This finding suggests a proteinase-resistance mechanism for non-mucin PM proteins to function in the proteinase rich gut environment. Immunohistochemical analysis showed that CBP1 and CBP2 are specifically localized in the PM. However, intact CBP1 and CBP2 proteins were not present in the PM, indicating that their partially degraded fragments were assembled into the PM. This observation suggests that the presence of a large number of chitin binding domains in PM proteins allows the proteins to tolerate limited proteolytic degradation in the midgut without loss of their chitin binding activity with multiple chitin binding domains. Alignment of the chitin binding sequences suggested that CBP1 and CBP2 evolved by gene duplication and the tandem chitin binding domains in the proteins arose from domain duplications.
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PMID:Identification of two new peritrophic membrane proteins from larval Trichoplusia ni: structural characteristics and their functions in the protease rich insect gut. 1487 18

Assessment of the mucin subclasses in the gastric juices of severe chronic rheumatoid arthritis (RA) patients was compared with non-RA cases which received the eradication treatment of Helicobacter pylori (H. pylori). Gastric juice samples were obtained from 8 RA patients (5 for H. pylori-negative and 3 for H. pylori-positive) and 5 control subjects in which we confirmed the successful eradication of H. pylori. The gastric luminal mucins were extracted and isolated by the ethanol precipitation method. These mucin solutions were digested with chymotrypsin, dialyzed, lyophilized, and redissolved. The obtained specimen was applied to an ion exchange column containing DEAE-Sepharose CL-6B and eluted with a discontinuous salt gradient in three salt steps. The gastric luminal mucins were divided into three fractions based on the distinctive sialic acid content. The proportion of acidic mucin rich in sialic acid from the gastric juice of RA patients without the H. pylori infection was significantly lower than those RA patients with H. pylori or the control subjects. A decrease in the acidic mucin content after eradication of H. pylori was commonly observed in all the control subjects. Our investigation raises the possibility that the gastric mucosae of RA patients have resistance against H. pylori infection. And the analysis of the composition in the gastric luminal mucin may be a very useful tool for the evaluation of gastric homeostasis in RA patients.
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PMID:Analysis of mucin composition in gastric juices of chronic rheumatic patients with upper gastrointestinal damage. 1615 30

The StcE zinc metalloprotease is secreted by enterohemorrhagic Escherichia coli (EHEC) O157:H7 and contributes to intimate adherence of this bacterium to host cells, a process essential for mammalian colonization. StcE has also been shown to localize the inflammatory regulator C1 esterase inhibitor (C1-INH) to cell membranes. We tried to more fully characterize StcE activity to better understand its role in EHEC pathogenesis. StcE was active at pH 6.1 to 9.0, in the presence of NaCl concentrations ranging from 0 to 600 mM, and at 4 degrees C to 55 degrees C. Interestingly, antisera against StcE or C1-INH did not eliminate StcE cleavage of C1-INH. Treatment of StcE with the proteases trypsin, chymotrypsin, human neutrophil elastase, and Pseudomonas aeruginosa elastase did not eliminate StcE activity against C1-INH. After StcE was kept at 23 degrees C for 65 days, it exhibited full proteolytic activity, and it retained 30% of its original activity after incubation for 8 days at 37 degrees C. Together, these results show the StcE protease is a stable enzyme that is probably active in the environment of the colon. Additionally, k(cat)/K(m) data showed that StcE proteolytic activity was 2.5-fold more efficient with the secreted mucin MUC7 than with the complement regulator C1-INH. This evidence supports a model which includes two roles for StcE during infection, in which StcE acts first as a mucinase and then as an anti-inflammatory agent by localizing C1-INH to cell membranes.
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PMID:Characterization of the StcE protease activity of Escherichia coli O157:H7. 1678 73


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