Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serpin-enzyme complex (SEC) receptor mediates catabolism of alpha 1-antitrypsin (alpha 1-AT)-elastase complexes and increases in synthesis of alpha 1-AT in cell culture. The SEC receptor recognizes a pentapeptide domain on alpha 1-AT-elastase complexes (alpha 1-AT 370-374), and the same domain in several other serpins, amyloid-beta peptide, substance P, and other tachykinins. Thus, it has also been implicated in the biological properties of these ligands, including the neurotoxic effect of amyloid-beta peptide. In this study, we examined the possibility that the SEC receptor mediates the previously described neutrophil chemotactic activity of alpha 1-AT-elastase complexes, and whether the other ligands for the SEC receptor have neutrophil chemotactic activity. The results show that 125I-peptide 105Y (based on alpha 1-AT 359-374) binds specifically and saturably to human neutrophils, and the characteristics of this binding are almost identical to that of monocytes and hepatoma-derived hepatocytes. Peptide 105Y and amyloid-beta peptide mediate chemotaxis for neutrophils with maximal stimulation at 1-10 nM. Mutant or deleted forms of peptide 105Y, which do not bind to the SEC receptor, have no effect. The neutrophil chemotactic effect of alpha 1-AT-elastase complexes is blocked by antiserum to peptide 105Y and by antiserum to the SEC receptor, but not by control antiserum. Preincubation of neutrophils with peptide 105Y or substance P completely blocks the chemotactic activity of amyloid-beta peptide, but not that of FMLP. These results, therefore, indicate that the SEC receptor can be modulated by homologous desensitization and raise the possibility that pharmacological manipulation of this receptor will modify the local tissue response to inflammation/injury and the neuropathologic reaction of Alzheimer's disease.
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PMID:The serpin-enzyme complex (SEC) receptor mediates the neutrophil chemotactic effect of alpha-1 antitrypsin-elastase complexes and amyloid-beta peptide. 132 93

By acid extraction, ethanol precipitation, affinity chromatography on 4-phenylbutylamine-Sepharose 4B and gel filtration on Sephadex G-100, calf liver neutral proteinase was purified. The purified enzyme was electrophoretically homogeneous and over 2000 times more active than the starting homogenate. The molecular weight, determined by SDS electrophoresis, was calculated as 27000. The pH optimum of the enzyme for whole calf thymus histones and N-benzoyltyrosine, ethyl ester (BTEE) was at 7.0 and 7.0-7.5. The Km value for histones was 2% and for BTEE 1.66 mM. The enzyme was strongly inhibited by soya-bean trypsin inhibitor and leucocyte intracellular I-1A inhibitor and less by alpha 1-antitrypsin and leucocyte inhibitor I-1B. The enzyme hydrolyzed only selected protein substrates, such as total thymus histones, Lys-rich histones, nucleoprotein and substance P, but not Arg-rich histones, hemoglobin and casein. The enzyme showed chymotrypsin-like properties by cleavage of substance P at the carboxyl groups of phenylalanine and leucine.
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PMID:The isolation of liver serine proteinase by affinity chromatography on 4-phenylbutylamine-sepharose 4 B. 705 3

Ragweed (Ambrosia artemisiifolia), the major cause of late summer hay fever (allergic rhinitis) in the United States and Canada, is clinically the most important source of the seasonal aeroallergens. A novel endopeptidase was extracted from the pollen of this plant and purified by a series of column chromatographic steps. It has a molecular mass of 82 kDa according to gel filtration and SDS-polyacrylamide gel electrophoresis and a pH optimum near 9.0, and its activity is unaffected by chelating or reducing agents. A 17-amino acid amino-terminal sequence of this protein showed no similarity with any other proteases. The enzyme was inhibited by diisopropyl fluorophosphate, a general serine class inhibitor, and more specifically N-p-tosyl-L-phenylalanine chloromethyl ketone, a chymotrypsin-like proteinase inhibitor. Various synthetic substrates were efficiently cleaved with a strong preference for Phe in the P1 and P3 position and Pro in the P2 position. This specificity was confirmed through inhibition studies with both peptidyl chloromethyl ketone and organophosphate inhibitors. In addition to synthetic substrates, the neuropeptides, vasoactive intestinal peptide and substance P, which are required for normalized lung functions, were also rapidly hydrolyzed. Activity toward protein substrates was not detected with the exception of the inactivation of alpha-1-proteinase inhibitor, which occurred through cleavage within the reactive site loop. These results indicate that the purified enzyme is a novel endopeptidase, which may be involved in both the degradation of neuropeptides and the inactivation of protective proteinase inhibitors during pollen-initiated allergic reactions.
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PMID:Purification and characterization of a novel endopeptidase in ragweed (Ambrosia artemisiifolia) pollen. 882 72

Extracts from ragweed pollen grains contain novel trypsin and chymotrypsin-like serine peptidases which are described in this report. The molecular mass of the chymotrypsin-like enzyme was 82 kDa, had a pH optimum near 9.0, and its activity was unaffected by chelating or reducing agents. It was inhibited by diisopropyl fluorophosphate (DFP), a general serine class inhibitor, and more specifically N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a chymotrypsin-like proteinase inhibitor. In addition to various synthetic substrates, the neuropeptides, vasoactive intestinal peptide (VIP) and substance P, which are required for normalized lung functions, were also rapidly hydrolysed. Activity toward protein substrates was not detected with the exception of the inactivation of alpha-1-proteinase inhibitor (alpha-1-PI) which occurred through cleavage within the reactive site loop. The 'trypsin-like' enzyme has a molecular mass near 80 kDa, a blocked N-terminus, a pH optimum near 9.0, and requires Ca++ for stability and activity, but not reducing agents. It is inhibited by DFP, and more specifically the trypsin-like proteinase inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK). Again, activity toward protein substrates was not detected, but various synthetic substrates and biologically active peptides were efficiently cleaved. Significantly, atrial natriuretic peptide (ANP) and angiotensin 2 (ATII), whose degradation would amplify kinin activity and influence inflammatory diseases of the respiratory tract and nasal passages, were also rapidly hydrolyzed.
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PMID:Ragweed pollen proteolytic enzymes: possible roles in allergies and asthma. 946 75