Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A group of active-site metal coordinating inhibitors of zinc proteases (carboxypeptidase A, thermolysin, Bacillus cereus neutral protease, and angiotensin-converting enzyme) have been synthesized and their properties investigated. Their general structures are R-SH and R-NH-PO2(O phi)H, where-S- or -O- serve as metal ligands and R refers to an amino acid or peptide group designed to interact with substrate recognition sites. These inhibitors can be extremely potent; thus, N-(2-mercaptoacetyl)-D-phenylalanine, e.g., inhibits carboxypeptidase A with a Kiapp of 2.2 x 10(-7) M. The spectral response of cobalt(II)-substituted thermolysin or carboxypeptidase A to the sulfur-containing inhibitors signals the direct interaction of the mercaptan with the metal. An S leads to Co(II) charge transfer band is generated near 340 nm and is detected by absorption, circular dichroism, and magnetic circular dichroism. The cobalt(II) spectra indicate both inner sphere coordination with sulfur and 4-coordination in the enzyme-inhibitor complex. Thus, the metal undergoes a simple substitution reaction, the inhibitor most likely displacing water at the fourth coordination site.
Proc Natl Acad Sci U S A 1979 Dec
PMID:Metal-coordinating substrate analogs as inhibitors of metalloenzymes. 23 May 2

Mating factor is a peptide excreted into the culture fluid by alpha-mating type cells of Saccharomyces cerevisiae X-2180 1B. The purification of the mating factor was carried out by ion exchange chromatography on phosphocellulose and Amberlite IRC 50 columns, followed by gel filtration on a Sephadex LH 20 column. The factor thus prepared was a peptide composed of Lys1, His1, Trp2, Gln2, Pro2, Gly1, Met1, Leu2 and Tyr1, and was able to induce morphological changes on alpha-mating type cells at a concentration of 5 pg/ml. The amino acid sequence of the mating factor was determined by the manual Edman degradation method using intact mating factor and its thermolytic peptides. The C-terminal amino acid residue was determined by digesting the factor with carboxypeptidase A. The complete amino acid sequence of the mating factor was established to be as follows: Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr.
J Biochem 1977 Dec
PMID:Purification and amino acid sequence of mating factor from Saccharomyces cerevisiae. 34 Apr 52

Five patients with asthma and severe aspirin hypersensitivity were challenged on separate days with increasing doses of aspirin given by mouth, starting with 5 mg, until a reduction in FEV1 greater than 15% was obtained. Sodium cromoglycate in doses of 20-40 mg inhibited the bronchoconstrictive reaction not only when inhaled before the challenge but also after it, at a time when progressive reduction in FEV1 values was taking place. According to these results, it seems reasonable to postulate sequential mast cell degranulation and liberation of mediators of anaphylaxis as the mechanism through which aspirin induces bronchoconstriction in aspirin-sensitive asthmatics. The differences between bronchial provocation tests and oral challenge with aspirin are stressed.
Thorax 1977 Dec
PMID:Inhibition of aspirin-induced bronchoconstriction by sodium cromoglycate inhalation. 41 71

Heparin as measured by azure A metachromasia and anticoagulant activity has been extracted with 1 M NaCl from (35)S-labeled human lung fragments or dispersed human lung cells enriched for mast cells. The (35)S-labeled metachromatic material in the 3 M NaCl eluate from Dowex-1 chromatography of the extract from lung fragments exhibited an average mol wt of 20,000 by Sepharose 4B gel filtration. The (35)S-labeled metachromatic material with the charge characteristics of commercial porcine heparin on DEAE cellulose chromatography was entirely heparin by the criteria of resistance to degradation by chondroitin ABC lyase and complete degradation by purified heparinase. Antithrombin affinity chromatography of purified heparin with an anticoagulant activity of 137 U/mg, revealed that the one-third that was bound and eluted had a 273 U/mg sp act, whereas the unbound activity was 31 U/mg. Thus, the previously observed heterogeneity of commercial porcine heparin for binding to human antithrombin was also observed with human heparin. The mast cell-enriched human lung cell preparations yielded [(35)S]mucopolysaccharides with an average mol wt of 60,000 by Sepharose 4B gel filtration. Approximately 30% of this fraction was degraded by chondroitin ABC lyase, and the residual 70% was degraded by purified heparinase. When the chondroitin ABC lyase-resistant fraction was subjected to alkali degradation the average mol wt was reduced to 20,000. The calculated human lung mast cell heparin content of 2.4-7.8 mug/10(6) cells gave a ratio to histamine on a weight basis similar to that of intact lung fragments, thereby implying that heparin in the lung fragments was largely restricted to the mast cells.
J Clin Invest 1979 Dec
PMID:Isolation and characterization of heparin from human lung. 50 Aug 22

The residues 90-92 can be split off from the C-terminal region of the isolated alpha-subunit of choriogonadotropin (residues 88--92: -Tyr-Tyr-His-Lys-Ser-OH) by means of serine carboxypeptidase (des-Lys91,Ser92-alpha-subunit; des-(90-92)-alpha-subunit). However, when choriogonadotropin is digested by serine carboxypeptidase, only the residues 143-145 (-Leu-Pro-Gln-OH) form the C-terminus of the beta-subunit are released (des-(143-145)-choriogonadotropin). Depending on the pH conditions, glutamine 145 and the residues 143-145, respectively, are liberated by digestion of the isolated beta-subunit (des-Gln145-beta-subunit and des-(143-145)-beta-subunit, respectively). The present study provides evidence that the C-termini of both the isolated subunits and those in choriogonadotropin are probably arranged on the surface of the molecules. The biological activity of des-(143-145)-choriogonadotropin is not significantly decreased. The immunological activity, however, is reduced when measured by complement fixation. In comparison to the native hormone, a four-fold amount of des-(143-145)-choriogonadotropin has to be applied to obtain highest complement fixation. The conformation of des-(143-145)-choriogonadotropin does not seem to differ from that of the native hormone, when estimated both by CD measurements and by Ans-choriogonadotropin fluorescence. The respective determinant therefore seems to depend, at least to some extent, on the sequence of the C-terminal region of the beta-subunit of the hormone; complement fixation, however, does not seem to be affected significantly, when the des-(143-145)-beta-subunit is compared with the native beta-subunit using an antiserum against the native beta-subunit. This provides evidence that this C-terminal determinant is possibly more immunogenic at the hormone than at the isolated beta-subunit. The biological activity of recombined choriogonadotropin in vivo as well as in vitro is markedly reduced when serine 92 is removed from the C-terminus of the alpha-subunit (des-Ser92,Lys91-alpha-native beta-subunit: 36% residual activity in vivo). Biological activity is lost when the residues 88-90 are removed by digestion of the des-Ser92,Lys91-alpha-subunit with carboxypeptidase A. Recombination products between a modified alpha-and the native beta-subunit show a reduced Anschoriogonadotropin fluorescence (des-Lys91,-Ser92-alpha + native beta-subunit: 52%; des-(88-92)-alpha- + native beta-subunit: 23%). The Ans-induced aggregation of choriogonadotropin, however, also takes place in those recombination products which display a low Ans-choriogonadotropin fluorescence, indicating that the reduction is probably not caused by a portion of the molecules losing their binding sites for Ans. Therefore the diminished Ans-choriogonadotropin fluorescence seems to signal small conformational changes. The CD spectra of the native and the des-(90-92)-alpha-subunit, however, seem not to differ significantly. It is shown that the release of amino acids from the C-terminus of the alpha-subunit causes a disturbance of the interaction between the subunits. This seems to prevent an effective conformational change of the beta-subunit which probably is a prerequisite for the binding of the hormone to the receptors of Leydig cells.
Hoppe Seylers Z Physiol Chem 1979 Dec
PMID:Studies of the specific role of the subunits of choriogonadotropin for biological, immunological and physical properties of the hormone. Digestion of choriogonadotropin and its isolated subunits with serine carboxypeptidase. 52 40

The catalytic concentrations of lipase and carboxypeptidase A in sera of patients with and without pancreatic diseases show no correlation. 40 sera out of 44 with elevated values for lipase, derived from a collective of 135 different sera, showed no increase in the catalytic concentrations of carboxypeptidase A. The demanding titrimetric determination of lipase cannot be replaced by the more simple colorimetric determination of carboxypeptidase A for the laboratory diagnosis of pancreatic diseases.
J Clin Chem Clin Biochem 1979 Dec
PMID:[Lipase and carboxypeptidase A in human serum: no correlation (author's transl)]. 54 41

Radioallergosorbent tests (RAST(s)) have been developed and assessed for the diagnosis of insect hypersensitivity by using a purified allergen from honeybee venom, phospholipase A, and crude yellow jacket venom. Sera from 193 patients positive both by history and skin test to one of these insects were compared with various groups of control sera. Eighty percent of sera from skin test-positive patients were RAST positive; positive RAST were found in 16% of sera tested from skin test-negative patients. A highly positive RAST correlates well with a positive skin test and clinical sensitivity, but serum IgE is not measurable in many patients with mast cell or basophil bound antibody. Since biologically important reactions of antigen with IgE require that the antibody be cell bound, skin testing would be preferred to RAST if one were limited to a single test for the diagnosis of insect allergy.
J Immunol 1978 Dec
PMID:Allergy to insect stings. IV. Diagnosis by radioallergosorbent test (R.A.S.T.). 56 72

In the presence of Ca2+ and Mg2+, the chemotactic fragment of C5, the synthetic chemotactic oligopeptide formyl-methionyl-leucyl-phenyl-alanine, and the ionophore A23187 aggregated human neutrophils. Aggregation induced by the two chemotactic factors was transient and reversed within 2 to 4 minutes after exposure; aggregation induced by A23187 was sustained and continued to increase over 15 minutes. In the absence of the bivalent cations, none of these three agents aggregated the cells. If bivalent cations were added after cell contact with a chemotactic factor, aggregation was detected after, but not before, addition of the cations. Under these conditions, the magnitude of the aggregation response was sharply reduced: cells preincubated with a chemotactic factor for longer than 2 to 4 minutes aggregated minimally after addition of bivalent cations. Moreover, cells preincubated with a chemotactic factor for 4 minutes, exposed to bivalent cations, and then rechallenged with the same chemotactic factor also showed a minimal aggregation response, ie, the cells were "desensitized" to the original stimulus. However, cells desensitized to one of the chemotactic factors still aggregated prominently when exposed to the other chemotactic factor or to A23187. Cells could not be desensitized to the ionophore A23187. Desensitization of the neutrophil aggregation response closely resembles desensitization of mast cell and leukocyte degranulation. Degranulation and aggregation appear to be closely related cellular responses to immunologic stimuli. Both responses may reflect alterations in surface membrane permeability to bivalent cations and/or changes in surface membrane adhesiveness to other biologic membranes.
Am J Pathol 1978 Dec
PMID:Desensitization of the neutrophil aggregation response to chemotactic factors. 71 43

The involvement of IgG2a antibodies and mast cells in antibody-dependent eosinophil cytotoxicity suggested a possible interaction between mast cells and eosinophils for in vitro killing of Schistosoma mansoni schistosomula. Cell purification procedures showed that a minimum ratio of mast cells was required to obtain eosinophil cytotoxicity. The incubation of mast cells with heat-aggregated IgG2a immunoglobulins before addition to a mast cell-depleted eosinophil population induced a significant degree of inhibition of cytotoxicity, Similarly, the heat-aggregated IgG2a Fc fragment had a strong inhibitory effect whereas incubation of mast cells with Fab fragment failed to inhibit the cytotoxic effect. The Fc portion of IgG2a immunoglobulins therefore seemed to be involved in binding to the mast cell surface. Furthermore, it was demonstrated that soluble mediators released after mast cell activation either by compound 48/80, or by IgE, or IgG2a-dependent reaction had the same effect as intact mast cells. These observations suggest that the eosinophil-dependent cytotoxicity mechanism requires a signal provided by soluble mast cell mediators in addition to antibody.
J Immunol 1978 Dec
PMID:Rat mast cell-eosinophil interaction in antibody-dependent eosinophil cytotoxicity to Schistosoma mansoni schistosomula. 72 83

The interaction of human plasma alpha-1-antichymotrypsin with serine proteinases from different tissues has been investigated. The protein was found to form stable complexes with pancreatic chymotrypsin, leukocyte cathepsin G, and mast cell chymotrypsin. No inhibition of pancreatic trypsin or leukocyte elastase could be demonstrated. With mixtures containing both alpha-1-antichymotrypsin and alpha-1-proteinase inhibitor, it was found that the former preferentially inactivated leukocyte cathepsin G, while the latter showed a strong preference for pancreatic chymotrypsin. However, leukocyte elastase was specifically inactivated by alpha-1-proteinase inhibitor even in 1:1 mixtures with chymotrypsin. All of these results taken together suggest that one of the primary functions of alpha-1-antichymotrypsin is to inactivate leukocyte cathepsin G, while alpha-1-proteinase inhibitor controls the activity of other serine proteinases, particularly leukocyte elastase.
Biochemistry 1978 Dec 26
PMID:Human alpha-1-antichymotrypsin: interaction with chymotrypsin-like proteinases. 72 23


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