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)

The spin-lattice and spin-spin relaxation rates were measured of the Gly C alpha and Tyr aryl protons of glycyl-L-tyrosine (Gly-Tyr) bound to manganese(II)-substituted carboxypeptidase A (MnCPA) in aqueous solution. The temperature and frequency dependences of the relaxation rates were analyzed using the Solomon-Bloembergen-Morgan equations. The binding modes of MnCPA with Gly-Tyr in solution are different from that of ZnCPA in crystals. 1. Mn(II)-coordinated water of MnCPA is not excluded by the binding of Gly-Tyr substrate molecules. 2. The Gly carbonyl group does not coordinate tightly to the metal ion of MnCPA. The Gly C alpha protons of Gly-Tyr in the productive binding site are appreciably mobile. 3. A non-productive loose binding of another Gly-Tyr molecule is suggested by simulation of the temperature and frequency dependences of the proton relaxation rates.
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PMID:Nuclear magnetic relaxation study on the interaction of glycyl-L-tyrosine with manganese-carboxypeptidase A in solution. 50 May 77

Microtubules from the cow adrenal cortex and brain were purified by three cycles of the temperature-dependent polymerization-depolymerization procedure. Whereas tubulin comprised approximately 8--10% of soluble brain protein, it comprised only 0.5-1.0% of the soluble adrenocortical protein. The partially purified tubulin from both sources gave similar results in the following studies: (1) [3H]colchicine binding examined by Scatchard analysis revealed an apparent Ka of 1 . 10(6) M-1 and a colchicine/tubulin molar binding ratio of 0.4-0.6; (2) tyrosylation studies using a specific tubulin-tyrosine ligase (which adds a tyrosine residue to the C-terminal glutamate or glutamine of the alpha-chain) in conjunction with carboxypeptidase A (which recovers the tyrosine) and (3) amino acid analysis. Examination of protein bands, in addition to the tubulin doublet of 55 000 molecular weight, on sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a difference between the two tubulin preparations. The adrenocortical preparation had protein bands corresponding to apparent molecular weight of 36 000, 60 000, and 68 000. In contrast the brain preparation had only proteins of molecular weights greater than 200 000 (these bands were absent in all adrenal preparations). It would thus appear that if proteins which copurify with tubulin through repeated cycles of polymerization-depolymerization play a role in either microtubule formation or function there is a distinct difference between neural and non-neural tissue.
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PMID:Purification of bovine adrenocortical and brain tubulin. A comparative study. 50 97

The carbonyl terminal tripeptide sequence of bradykinin (Pro-Phe-Arg) is molecularly manipulated to obtain agents with potent antagonistic activity towards the smooth muscle contractile activity of bradykinin. Screening of various peptide derivatives revealed that heptyl amides or esters of H-D-Pro-Phe-Arg, and H-D-Phe-Phe-Arg possessed relatively stronger antibradykinin activity on the isolated smooth muscle preparation. The parent tripeptides, H-D-Pro-Phe-Arg-OH, and H-D-Phe-Phe-Arg-OH, and their amino acid components, i.e. D-Proline, D-Phenylalanine, L-Phenylalanine and Arginine, did not possess any antibradykinin activity in concentrations of up to 10(-4) M. When the heptyl derivatives of these peptides were incubated with either heparinized or citrated whole blood or plasma, the antibradykinin activity was not lost. Incubation of these peptide derivatives with either carboxypeptidase A or B did not result in any loss of the pharmacological effect. However, pancreatic protease extract produced a significant loss of the anti-oxytocic action on the isolated rat uterus preparation. H-D-Pro-Phe-Arg-NH-lauryl derivative also blocked the action of bradykinin and this effect sustained for a longer period of time comparative to the blockade with H-D-Pro-Phe-Arg-NH-heptyl derivative. In concentrations of 10(-7) M and 10(-8) M and 1 min incubation, which blocked the contractile action of bradykinin (1 nmole) on the isolated guinea pig ileum, these peptide derivatives did not block the action of acetylcholine, histamine, and serotonin. However, in concentrations of about 10(-6) M and higher with 5 min. incubation histamin is also blocked. On the isolated rat uterus preparation the contractile action of acetylcholine, angiotensin, oxytocin and vasopressin was blocked at concentrations of 10(-6) M. These findings warrant a differential pharmacological evaluation and in vivo testing of these peptide derivatives to investigate their therapeutic potential.
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PMID:Inhibition of the contractile action of bradykinin on isolated smooth muscle preparations by derivatives of low molecular weight peptides. 51 62

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.
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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.
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PMID:[Lipase and carboxypeptidase A in human serum: no correlation (author's transl)]. 54 41

Coupling of bovine carboxypeptidase A with diazotized 5-amino-1H-tetrazole increases esterase activity, decreases peptidase activity slightly, and modifies one tyrosyl residue. Subsequent nitration of the azoenzyme has no further effect on esterase activity, decreases peptidase activity markedly, and modifies a second tyrosyl residue. Analysis of the azopeptides isolated from a chymotrypsin digest of the doubly modified enzyme by affinity, ion exchange, and high pressure liquid chromatography indicates that the principal residue modified by diazo-1H-tetrazole is Tyr-248. Analysis of the nitropeptides isolated by similar procedures indicates that nitration occurs mainly at Tyr-198. This residue becomes susceptible to modification only as a consequence of a conformational change that accompanies azo coupling of Tyr-248. These results describe a unique example of the influence of protein structure on the reactivity of functional amino acid residues and illustrate an important aspect of chemical modification of enzymes.
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PMID:Functional tyrosyl residues of carboxypeptidase A. The effect of protein structure on the reactivity of tyrosine-198. 56 10

Effects of proteinase inhibitors on total proteolytic activity and trypsin and chymotrypsin activity in human pancreatic juice were determined separately. Purified inhibitors as well as crude extracts of raw soybeans completely inhibited trypsin and chymotrypsin activity while 40 to 50% of the total proteolytic activity remained. Inhibition experiments with 1,10-o-phenanthroline showed that this residual proteolytic activity was due mainly to carboxypeptidase A and B. Comparative studies with rat pancreatic enzymes demonstrated certain similarities between the corresponding enzymes from rat and man. However, differences were revealed which indicate that the rat enzymes must be used with great caution when applied as models for the human proteinases when studying effects of soybean inhibitors.
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PMID:Inhibition of human and rat pancreatic proteinases by crude and purified soybean proteinase inhibitors. 57 Oct 12

A series of monocarboxylic and dicarboxylic acid sulfur-containing by-product analogues of lysine and arginine has been synthesized and tested as competitive inhibitors of bovine carboxypeptidase B. The most effective derivatives were guanidinoethylmercaptosuccinic acid and aminopropylmer-captosuccinic acid with Kis of 4 and 8 X 10(-6) M, respectively. Kinetics studies established the pure competitive nature of the inhibition. Mixed studies with the alkylating reagents bromoacetyl-D-arginine and bromoacetamidobutylguanidine established their efficiency in protecting the active-center glutamic acid and tyrosine of bovine carboxypeptidase B, respectively, from irreversible alkylation. Kinetic studies with bovine carboxypeptidase A and porcine carboxypeptidase B showed a lack of efficiency for A and high degree of efficiency for B.
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PMID:By-product analogues for bovine carboxypeptidase B. 61 98

3,3-Diphenylpropanoate (DPP) activates the carboxypeptidase A catalyzed hydrolysis of benzoylglycyl-L-phenylalanine (BzGly-L-Phe) (Ka = 2.1 x 10 (-3) M) and inhibits ester hydrolysis uncompetitively (K1 =2.1 X 10 (-3) M). A common modifier binding site located adjacent to the peptide and ester substrate binding sites is proposed. The forms of the pathways proposed for activation and inhibition are remarkably similar.
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PMID:Mechanisms for activation and inhibition of carboxypeptidase A catalyzed hydrolyses of peptides and esters. 66 84

Properties of carboxypeptidase A of cultured skin fibroblasts from control and cystic fibrosis patients were studied using alpha-N-carbobenzoxy-L-glutamyl-L-tyrosine as substrate. Carboxypeptidase A was inhibited by thiomersal, cyanide, iodoacetate and N-ethylmaleimide in a similar manner for control and cystic fibrosis fibroblasts. Both trypsin and dithiothreitol treatment activated the enzyme, but 1,10-phenanthroline inhibited only in the presence of dithiothreitol. Both Zn2+ and Co2+ reversed this inhibition. Trypsin treatment of carboxypeptidase A produced a form of the enzyme having a higher KM value for both control and cystic fibrosis fibroblasts. Dithiothreitol treatment of control fibroblasts resulted in a form with similar properties to the trypsin activated form, but cystic fibrosis fibroblasts yielded a variant form with even higher KM and Vmax values. Since other properties were similar, it seems likely that this difference reflected binding of a molecule to the enzyme rather than of a defect in the enzyme.
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PMID:Carboxypeptidase A activity of cultured skin fibroblasts and relationship to cystic fibrosis. 66 47


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