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

35Cl minus-nuclear magnetic resonance (NMR) studies indicate that various digests of human hemoglobin with carboxypeptidase A and B, or a combination of the two, may be used for the identification of chloride binding sites. All the digestion products contain, like hemoglobin itself, at least two classes of binding sites, one of high, the others of low affinity. The pH dependence of the excess linewidth of the 35Cl minus NMR signal indicates that in the simple digests with either carboxypeptidase A or B, chloride is bound with high affinity at or near His-beta146-Asp-beta94 and at or near Val-alpha1-Arg-alpha141. The high-affinity sites show, in the case of the simple digests, a strong oxygen linkage which is lost in the forms digested with both carboxypeptidase A and B; this linkage may thus be correlated to the presence of conformational changes. Organic phosphates, like inositol hexaphosphate, show competition for some of the high-affinity chloride binding sites in hemoglobin and in the simple digests. This competition is likewise lost in the doubly digested hemoglobins.
 ...
PMID:Identification of chloride-binding sites in hemoglobin by nuclear-magnetic-resonance quadrupole-relaxation studies of hemoglobin digests. 0 Feb 36

The O2 binding properties of sulfhemoglobin were studied. The oxygen tension required for half-saturation of sulfhemoglobin is more than 2 orders of magnitude higher than that for hemoglobin A. The binding of O2 exhibits an alkaline Bohr effect larger than that observed for hemoglobin, yet the Hill number is unity. From the Bohr titration curve, 0.68 proton is released during O2 binding at 0 degrees C. Sulfhemoglobin prepared from carboxypeptidase A-treated hemoglobin has an affinity for O2 which is about the same as that of sulfhemoglobin at the theoretical limit of the Bohr titration curve. Like its carboxypeptidase A-treated hemoglobin precursor, this sulfhemoglobin does not bind O2 cooperatively. Thus, sulfhemoglobin appears to be in a high affinity form at alkaline pH and a low affinity form at acid pH, similar to hemoglobin A. These results demonstrate that the magnitude of the Hill number is not always an indicator of the interaction between oxygen binding and other functions in a hemoglobin.
 ...
PMID:The reversible binding of oxygen to sulfhemoglobin. 2 95

The enzyme carboxypeptidase A has been extensively studied and is thus a good candiate for chemical models and imitation. A model system was constructec which combined two of the three catalytic functional groups of the enzyme together with the appropriate substrate group, and cooperative effective catalysis was demonstrated. However, the mechanism which the model system used in enzyme-like conditions was unexpected, and this led to a study of the enzyme itself. Carboxypeptidase A was studied by examination of oxygen-18 exchange reactions and the ability of the enzyme to substitute only lytic agents, such as methanol, forthe water which is normally used. The result of these studies is proposed mechanism of action of this enzyme which accommodates the large amount of information already available, and which indicates that this enzyme uses a mechanism similar to that found in the model system. Approaches have also been made to an artificial enzyme which could hydrolyse amides. Cyclodextrin has been functionalized with two imidazole groups placed on opposite sides of the cavity. This material catalyses the hydrolysis of an amide, which binds to the cyclodextrin cavity and then is hydrolysed with the assistance of one imidazole in its basic form and the other one in its protonated form, acting together in a way reminiscent of the cooperation of some of the functional groups of hydrolytic enzymes.
 ...
PMID:Studies on enzyme models and on the enzyme carboxypeptidase A. 24 79

The hemoglobin of the flatworm Dicrocoelium dendriticum, a lanceolate fluke which infests the hepatic ducts of certain mammals, has been isolated by gel filtration and ion-exchange chromatography. The molecular weight of the denatured protein was found to be 15500, a value in the same range as hemoglobin subunits. The fact that the native hemoglobin has an apparent molecular weight of 22000 in 0.01 M phosphate buffer, pH 7.4, suggests limited aggregation. The protein contains, as all other myoglobins and hemoglobins, one molecule of non-covalently associated ferroprotoporphyrin IX per polypeptide chain. It forms the same ligand derivatives with very similar spectral properties as vertebrate hemoglobins. The high oxygen affinity (p50 is 0.07--0.1 mmHg or 9.3--13.3 Pa at 20 degrees C and pH 7.0) and the absence of heme-heme interaction of (Hill coefficient nH=1.0) are properties which this heme protein shares with other monomeric hemoglobins from invertebrate and lower vertebrate organisms. The native hemoglobin exists in two forms, having isoelectric points of 4.51 and 4.53, which do not differ in their amino-acid compositions. Dansylation indicated that the amino-terminal amino-acid residue is alanine. The carboxy-terminal sequence, determined by carboxypeptidase A digestion of the globin, is -His-Ala-Leu.
 ...
PMID:Isolation and characterization of the hemoglobin from the lanceolate fluke Dicrocoelium dendriticum. 68 24

The enzymic hydrolysis of some proteins (insulin-B-chain-S-sulfonate, S-aminoethylated lysozyme, bovine serum albumin) by immobilized peptidolytic enzymes is reported. Sepharose-bound pronase, trypsin and a protease from Thermoactinomyces sp. (MP), the latter both cross linked by glutaric dialdehyde and an exopeptidase mixture containing Sepharose-bound leucine aminopeptidase, carboxypeptidase A and a crude preparation of prolidase were used. After enzymic hydrolysis nearly all amino acids, except proline, were recovered in a 100% yield compared to the value of an acid reference hydrolysate. Tryptophan and methionine, which are partially destroyed by acid hydrolysis in the presence of oxygen could be recovered completely.
 ...
PMID:[Protein hydrolysis by immobilized enzymes]. 98 21

Recent studies have demonstrated a connection between xanthine oxidase-generated reactive oxygen intermediates and histamine release during ischemia-reperfusion. In the present work, the effect of modulation of the endogenous histamine level on the xanthine oxidase activity was examined during the reperfusion of a canine ileal segment following a 2 hr of complete ischemia. The xanthine oxidase activity and the plasma histamine level peaked simultaneously at the beginning of reperfusion, reaching mean values of 14.9 nmol/ml/min and 12.1 nmol/l, respectively. Pretreatment with aminoguanidine, a blocker of diamine oxidase (histaminase), resulted in significantly higher levels of histamine during reperfusion, but this elevation was not accompanied by a further increase in xanthine oxidase activity. Pretreatment with the mast cell stabilizer cromolyn significantly diminished the rise in plasma histamine level, with an unchanging activity of xanthine oxidase. No significant alteration could be observed in the postocclusive activity of xanthine oxidase following the intra-arterial administration of 0.5, 1, or 5 nmol of histamine during the last 10 min of the ischemic period. These data suggest that the amount of histamine liberated during reperfusion does not result in a further increase in the xanthine oxidase activity. The release of histamine is not a cause, but rather an effect of the elevated activity of intestinal xanthine oxidase.
 ...
PMID:Studies on the relationship between xanthine oxidase and histamine release during intestinal ischemia-reperfusion. 138 3

Immunopathological studies of SIDS share the problems of all necropsy based studies of this syndrome: the extent of autolytic changes in the material under study; and the lack of appropriate controls. Despite these problems, several studies have been performed on serum, bronchoalveolar lavage, and pulmonary tissue. Many of these studies have been inspired by the modified anaphylaxis hypothesis, based on the experiments of Coombs and coworkers. Lightly anaesthetised guinea-pigs, which had been sensitised to cows' milk protein, were shown to die after intratracheal challenge. Studies of serum IgE concentrations in SIDS initially indicated raised specific IgE for Dermatophagoides pteronyssinus, Aspergillus fumigatus, and bovine beta-lactoglobulin, but subsequent studies have not sustained these findings. Raised immunoglobulin concentrations in bronchoalveolar lavage fluid have been found in association with SIDS but this probably reflects plasma leakage rather than local secretion. Immunocytochemical analysis of lavage cells performed by the same group revealed no major difference between SIDS cases and controls, although these were limited to four cases. To date, there have been no comprehensive studies of the inflammatory cell content of the pulmonary parenchyma in SIDS. In our own studies, we have examined the mast cell and eosinophil populations in the lungs of 49 cases of infants with SIDS and in 33 infants dying of non-pulmonary causes in the first 18 months of life. We found no difference in mast cell numbers between the groups but there was a striking excess of eosinophils in the lungs of infants dying of SIDS. Because eosinophils can secrete oxygen free radicals and cytotoxic cationic proteins, we regard this as evidence of a potential mechanism for the pulmonary oedema that is characteristic of SIDS. A viral infection which might otherwise have been trivial could therefore prove fatal.
 ...
PMID:Immunopathology of SIDS. 147 58

The molecular structures of three phosphorus-based peptide inhibitors of aspartyl proteinases complexed with penicillopepsin [1, Iva-L-Val-L-Val-StaPOEt [Iva = isovaleryl, StaP = the phosphinic acid analogue of statine [(S)-4-amino-(S)-3-hydroxy-6-methylheptanoic acid] (IvaVVStaPOEt)]; 2, Iva-L-Val-L-Val-L-LeuP-(O)Phe-OMe [LeuP = the phosphinic acid analogue of L-leucine; (O)Phe = L-3-phenyllactic acid; OMe = methyl ester] [Iva VVLP(O)FOMe]; and 3, Cbz-L-Ala-L-Ala-L-LeuP-(O)-Phe-OMe (Cbz = benzyloxycarbonyl) [CbzAALP(O)FOMe]] have been determined by X-ray crystallography and refined to crystallographic agreement factors, R ( = sigma parallel to F0 magnitude of - Fc parallel to/sigma magnitude of F0), of 0.132, 0.131, and 0.134, respectively. These inhibitors were designed to be structural mimics of the tetrahederal transition-state intermediate encountered during aspartic proteinase catalysis. They are potent inhibitors of penicillopepsin with Ki values of 1, 22 nM; 2, 2.8 nM; and 3, 1600 nM, respectively [Bartlett, P. A., Hanson, J. E., & Giannousis, P. P. (1990) J. Org. Chem. 55, 6268-6274]. All three of these phosphorus-based inhibitors bind virtually identically in the active site of penicillopepsin in a manner that closely approximates that expected for the transition state [James, M. N. G., Sielecki, A.R., Hayakawa, K., & Gelb, M. H. (1992) Biochemistry 31, 3872-3886]. The pro-S oxygen atom of the two phosphonate inhibitors and of the phosphinate group of the StaP inhibitor make very short contact distances (approximately 2.4 A) to the carboxyl oxygen atom, O delta 1, of Asp33 on penicillopepsin. We have interpreted this distance and the stereochemical environment of the carboxyl and phosphonate groups in terms of a hydrogen bond that most probably has a symmetric single-well potential energy function. The pro-R oxygen atom is the recipient of a hydrogen bond from the carboxyl group of Asp213. Thus, we are able to assign a neutral status to Asp213 and a partially negatively charged status to Asp33 with reasonable confidence. Similar very short hydrogen bonds involving the active site glutamic acid residues of thermolysin and carboxypeptidase A and the pro-R oxygen of bound phosphonate inhibitors have been reported [Holden, H. M., Tronrud, D. E., Monzingo, A. F., Weaver, L. H., & Matthews, B. W. (1987) Biochemistry 26, 8542-8553; Kim, H., & Lipscomb, W. N. (1991) Biochemistry 30, 8171-8180].(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Crystallographic analysis of transition-state mimics bound to penicillopepsin: phosphorus-containing peptide analogues. 160 44

The orientation of cytochrome b6 in the thylakoid membrane and the question of whether the number of membrane spanning helices is an even or odd number was tested through the relative trypsin susceptibility of epitopes (Asp-5 to Gln-14) and (Ile-205 to Leu-214) at the NH2 and COOH termini, respectively, of the 214-residue cytochrome b6 polypeptide. A structure of the cytochrome with an even number of helices and the NH2 and COOH termini on the stromal side of the membrane was inferred from the following: 1) cleavage of cytochrome b6 by trypsin added to thylakoids occurs by removal of both of the exposed NH2- and COOH-terminal epitopes. The epitopes at the termini were more sensitive to trypsin after prior treatment of thylakoids with carboxypeptidase A, indicating that these epitopes are shielded on the stromal side of the membrane by the COOH termini of other proteins. 2) Both epitopes were more trypsin-sensitive in thylakoid membranes than was cytochrome f that is only sensitive to trypsin acting on the lumen side of the membrane. 3) The NH2- and COOH-terminal epitopes of cytochrome b6 were also more sensitive to trypsin added to thylakoid membranes than were the oxygen-evolving complex 16- and 33-kDa proteins that are completely located on the lumen side. 4) The order of trypsin susceptibility was reversed in inside-out membranes, where the cytochrome NH2- and COOH-terminal epitopes were less sensitive than the 16- and 33-kDa proteins. The decreased relative sensitivity of the cytochrome b6 epitopes occurs in spite of a greater absolute sensitivity of these epitopes to trypsin in inside-out membranes. 5) The greater absolute sensitivity can be explained by a 4-helix model that includes trypsin-sensitive sites on the lumen side.
 ...
PMID:Thylakoid membrane protein topography. Location of the termini of the chloroplast cytochrome b6 on the stromal side of the membrane. 169 78

The structure of the carboxypeptidase A complex with the inhibitor (S)-(+)-1-amino-2-phenylethylphosphonic acid has been determined at 0.23 nm resolution. The delta F map shows electron-density peaks both in the S1 and S'1 sites, where the inhibitor molecule can be modeled in two different orientations with approximate 50% occupancy. In the proposed model, the phosphonate group binds to the zinc ion in a monodentate fashion. Other anchoring groups for the inhibitor molecule are Arg127 (hydrogen bonds with the phosphonate oxygen atoms) and Glu270 (hydrogen bond with the amino group in one of the two orientations). A recent spectroscopic investigation of the complex between cobalt(II) carboxypeptidase A and (S)-(+)-1-amino-2-phenylethylphosphonic acid is essentially in agreement with our results.
 ...
PMID:X-ray diffraction study of the interaction between carboxypeptidase A and (S)-(+)-1-amino-2-phenylethyl phosphonic acid. 173 Feb 23


1 2 3 4 5 6 7 8 9 10 Next >>