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 structures of the complexes of carboxypeptidase A with the amino acids D-phenylalanine and D-tyrosine are reported as determined by x-ray crystallographic methods to a resolution of 2.0 A. In each individual study one molecule of amino acids binds to the enzyme in the COOH-terminal hydrophobic pocket: the carboxylate of the bound ligand salt links with Arg-145, and the alpha-amino group salt links with Glu-270. The carboxylate of Glu-270 must break its hydrogen bond with the native zinc-bound water molecule in order to exploit the latter interaction. This result is in accord with spectroscopic studies which indicate that the binding of D or L amino acids (or analogues thereof) allows for more facile displacement of the metal-bound water by anions (Bicknell, R., Schaffer, A., Bertini, I., Luchinat, C., Vallee, B. L., and Auld, D. S. (1988) Biochemistry 27, 1050-1057). Additionally, we observe a significant movement of the zinc-bound water molecule (approximately 1 A) upon the binding of D-ligands. We propose that this unanticipated movement also contributes to anion sensitivity. The structural results of the current x-ray study correct predictions made in an early model building study regarding the binding of D-phenylalanine (Lipscomb, W. N., Hartsuck, J. A., Reeke, G. N., Jr., Quiocho, F. A., Bethge, P. H., Ludwig, M. L., Steitz, T. A., Muirhead, H., and Coppola, J. C. (1968) Brookhaven Symp. Biol. 21, 24-90).
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PMID:Binding of D-phenylalanine and D-tyrosine to carboxypeptidase A. 256 89

The complex of the 39-amino inhibitor (potato) of bovine carboxypeptidase A (carboxypeptidase; peptidyl-L-amino-acid hydrolase, EC 3.4.12.2) was crystallized in space group P32. There are two protein-inhibitor complexes in the asymmetric unit. These crystals exhibited pseudo-P3221 symmetry due to twinning about the a3 axis. Heavy atom difference Patterson maps and rotation functions indicated, however, that the noncrystallographic twofold axis that relates these two complexes is nearly coincident with the a3 axis. Consequently, to a good approximation at low resolution, the space group of the complex is P3221 and the effects of twinning may be ignored. The structure was solved by using multiple isomorphous replacement and molecular replacement techniques. At 5.5-A resolution, the multiple isomorphous replacement map was readily interpretable in terms of the known native carboxypeptidase A structure plus extra density around the active site. The position of this extra density is consistent with the binding mode for extended substrate proposed from earlier model building studies with the native enzyme (Lipscomb, W.N., Hartsuck, J.A., Reeke, G.N., Quiocho, F.A. Bethge, P.H., Ludwig, M.L., Steitz, T.A., Muirhead, H. & Coppola, J.C. (1968) Brookhaven Symp. Biol. 21, 24-90).
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PMID:Structure of potato inhibitor complex of carboxypeptidase A at 5.5-A resolution. 692 19

An x-ray diffraction study at 2.8 A resolution has yielded the structure of a complex between bovine carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and (-)-2-benzyl-3-p-methoxybenzoylpropionic acid. This substrate is an analogue of N-(p-methoxy)-benzoylphenylalanine, in which the amide NH is replaced by CN2. T. Sugimoto and E T. Kaiser (1979) J. Am. Chem. Soc. 101, 39469--3951] have shown that this complex catalyzes stereospecific exchange of that proton of the CH2 group which is in the R configuration. Our structure of this complex suports the model proposed by Sugimoto and Kaiser and is very similar to the productive peptide binding mode suggested by Lipscomb et al. [Lipscomb, W. N., Hartsuck, J. A., Reeke, G. N., Quiocho, F. A., Bethge, P. A., Ludwig, M. L., Steitz, T. A., Muirhead, H. & Coppola. J. C. (1968) Brookhaven Symp. Biol. 21, 24--90]. The proposed roles of glutamic acid 270 in the proton exchange and the interaction of zinc with the carbonyl group of the substrate are consistent with the observed structure.
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PMID:Structure of an actively exchanging complex between carboxypeptidase A and a substrate analogue. 693 21

A relationship has been suggested between mast cells (MCs) and male pattern hair loss (MPHL), because of histological evidence of perifollicular fibrosis and increased mast cell numbers. Two paired punch biopsies were taken from balding vertexes and non-balding occipital promontory areas of ten patients with MPHL (Ludwig-Hamilton IIIv to IV) and from five normal subjects aged from 20 to 35 years. Masson trichrome and Victoria blue staining were performed to observe collagen frameworks and elastic fiber structures. Numbers of immunoreactive MCs stained with anti-tryptase or anti-chymase antibody were counted. It was found that collagen bundles were significantly increased in balding vertexes than in non-balding occiput scalp skin. A near 4-fold increase in elastic fibers was observed in both vertex and occiput scalp skins with MPHL versus controls. Total numbers of MCs (tryptase-positive) in site-matched scalp samples were about 2-fold higher in MPHL subjects than in normal controls. Percentage elastic fiber (%) was found to be relatively well-correlated with tryptase and chymase-positive MCs. These findings suggest that accumulated MCs might be responsible for increased elastic fiber synthesis in MPHL, and indicate that future investigations are warranted.
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PMID:Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells. 1828 92