Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chromatin core particle DNA conformation deduced in broad outline by Finch et al. [Finch, J. T., Lutter, L. C., Rhodes, D., Brown, R. S., Rushton, B., Levitt, M. & Klug, A. (1977) Nature 269, 29-36] can be described in detail using other available experimental results. Histone binding sites compatible with the pattern of pancreatic DNase I digestion (Simpson, R. T. & Whitlock, J. P., Jr. (1976) Cell 9, 347-353; Noll, M. (1977) J. Mol. Biol. 116, 49-71; Lutter, L. C. (1977) J. Mol. Biol. 117, 53-69] lend to core particle DNA pseudosymmetry characteristic of molecular point group D(3). DNA symmetry and pseudosymmetry, in turn, imply equivalence and quasi-equivalence properties of the histone packing arrangement that support the following deductions: (i) One and only one alpha(2)beta(2) histone tetramer, presumably (H3)(2)(H4)(2), can serve as a stable subassembly within the histone octamer. (ii) There is a unique, strand-specific way to assign DNA binding domains to the arginine-rich histones (H3 and H4). (iii) Histones H3 and H4 alone should suffice to impose a supercoiled structure on DNA, as is observed experimentally, because only the tetramer can mimic a screw dislocation and thereby complement the screw symmetry of the DNA supercoil. (iv) The two slightly lysine-rich histones H2A and H2B are probably responsible, each in a different way, for dividing the eukaryotic chromatin fiber into discrete subunits. (v) The proposed arrangement of four distinct proteins appears to be a minimum formal requirement for making nucleosomes; that is, for introducing regularly spaced supercoiled DNA folds without also allowing formation of an indefinitely long (and genetically inert) DNA superhelix.
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PMID:Histone packing in the nucleosome core particle of chromatin. 27 80

Phagocytosis by monocytes or neutrophils can be enhanced by interaction with several proteins or synthetic peptides containing the Arg-Gly-Asp sequence. Recently we showed that an mAb, B6H12, specifically inhibited this enhancement of neutrophil phagocytosis by inhibiting Arg-Gly-Asp binding to the leukocyte response integrin (Gresham, H. D., J. L. Goodwin, P. M. Allen, D. C. Anderson, and E. J. Brown. 1989. J. Cell Biol. 108:1935-1943). Now, we have purified the antigen recognized by B6H12 to homogeneity. Surprisingly, it is a 50-kD molecule that is expressed on the plasma membranes of all hematopoietic cells, including erythrocytes, which express no known integrins. On platelets and placenta, but not on erythrocytes, this protein is associated with an integrin that can be recognized by an anti-beta 3 antibody. In addition, both the anti-beta 3 and several mAbs recognizing the 50-kD protein inhibit Arg-Gly-Asp stimulation of phagocytosis. These data demonstrate an association between integrins and the 50-kD protein on several cell types. For this reason, we call it Integrin-associated Protein (IAP). We hypothesize that IAP may play a role in signal transduction for enhanced phagocytosis by Arg-Gly-Asp ligands.
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PMID:Integrin-associated protein: a 50-kD plasma membrane antigen physically and functionally associated with integrins. 227 87

Avian liver mitochondrial hydroxymethylglutaryl-CoA synthase contains an active-site cysteine involved in forming the labile acetyl-S-enzyme intermediate. Identification of and assignment of function to this cysteine have been accomplished by use of an experimental strategy that relies upon generation and rapid purification of the S-acetylcysteine-containing active-site peptide under mildly acidic conditions that stabilize the thioester adduct. Automated Edman degradation techniques indicate the peptide's sequence to be Arg-Glu-Ser-Gly-Asn-Thr-Asp-Val-Glu-Gly-Ile-Asp-Thr-Thr-Asn-Ala-Cys-Tyr. The acetylated cysteine corresponds to position 129 in the sequence deduced from cDNA data for the hamster cytosolic enzyme [Gil, G., Goldstein, J.L., Slaughter, C.A., & Brown, M.S. (1986) J. Biol. Chem. 261, 3710-3716]. The acetyl-peptide sequence overlaps that reported for a tryptic peptide that contains a cysteine targeted by the affinity label 3-chloropropionyl-CoA [Miziorko, H. M., & Behnke, C. E. (1985) J. Biol. Chem. 260, 13513-13516]. Thus, availability of these structural data allows unambiguous assignment of the acetylation site on the protein as well as a refinement of the mechanism explaining the previously observed affinity labeling of the enzyme.
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PMID:Identification of the site of acetyl-S-enzyme formation on avian liver mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. 290 51

Three unique bilin peptides, a beta subunit peptide bearing a doubly linked phycourobilin (PUB), and two gamma subunit peptides with singly linked PUB groups, were obtained by enzymatic degradation of Gastroclonium coulteri R-phycoerythrin. These peptides were shown to have the sequences (Klotz, A. V., and Glazer, A. N. (1985) J. Biol. Chem. 260, 4856-4863): (Formula: see text) The sequence of peptide beta-3T was identical to that previously established for a doubly linked phycoerythrobilin (PEB) peptide derived from a B-phycoerythrin (Lundell, D. J., Glazer, A. N., DeLange, R. J., and Brown, D. M. (1984) J. Biol. Chem. 259, 5472-5480). Secondary ion mass spectrometry of beta-3T yielded a protonated molecular ion of 1629 mass units, the same as that given by the doubly linked PEB peptide (Schoenleber, R. W., Lundell, D. J., Glazer, A. N., and Rapoport, H. (1984) J. Biol. Chem. 259, 5481-5484), indicating that the doubly linked PUB and PEB tetrapyrroles were isomeric structures. High resolution 1H NMR analyses of peptides beta-3T, gamma-BV8, and gamma-DP provided unambiguous structural assignments for the singly and doubly linked PUB chromophores and indicated that the peptides in gamma-BV8 and gamma-DP were linked to ring A. The determination of which peptide fragment is linked to ring A and which to ring D in peptide beta-3T was not achieved in this study. 1H NMR analyses of three PEB-peptides from G. coulteri R-phycoerythrin--alpha-1 Cys(PEB)-Tyr-Arg, alpha-2 Leu-Cys(PEB)-Val-Pro-Arg, and beta-1 Met-Ala-Ala-Cys(PEB)-Leu-Arg--showed that they were identical to previously described corresponding chromopeptides from Porphyridium cruentum B-phycoerythrin, with the peptide linked to ring A of PEB in each instance (Schoenleber, R. W., Lundell, D. J., Glazer, A. N., and Rapoport, H. (1984) J. Biol. Chem. 259, 5485-5489). This is the first documented report on the structure of singly or doubly linked phycourobilins.
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PMID:Bilin attachment sites in the alpha, beta, and gamma subunits of R-phycoerythrin. Structural studies on singly and doubly linked phycourobilins. 383 47

Single capillaries in the mesenteries of pithed frogs were perfused sequentially with two frog Ringer solutions. The first solution contained no protein; the second solution contained either native or chemically modified bovine serum albumin (BSA) at a concentration of 3-5 mg ml-1. During each perfusion capillary permeability was assessed from the hydraulic conductivity of the capillary wall (Lp) which was determined from measurements of fluid filtration rate at two or more different capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974). Lp measured during perfusion with protein-free Ringer solution was on average three times greater than its value for the same vessel perfused with Ringer solution containing native BSA. This confirms the findings of Mason, Curry & Michel (1977). BSA, which had been succinylated to modify the free amino groups of its lysine residues, appeared to be as effective as native BSA in reducing Lp. After modification of its arginine side chains by exposure to 1,2-cyclohexanedione (CHD) in the presence of 0.2 M-NaOH, BSA lost its property of reducing Lp in capillaries perfused with Ringer solution. Exposure of BSA to 0.2 M-NaOH followed by dialysis against normal Ringer solution did not affect its property of reducing Lp. CHD-treated BSA at a concentration of 2.5 mg ml-1 had no effect upon the effective osmotic pressure exerted across capillary walls by Ringer perfusates containing the neutral polymer Ficoll 70 at a concentration of 40 mg ml-1. Native BSA raised the effective osmotic pressure from 7.07 +/- 1.93 cmH2O to 20.50 +/- 2.37 cmH2O (n = 7; P less than 0.001). It is concluded that the effects of BSA on permeability depend upon specific sites in the BSA molecule. It is suggested that these sites involve positively charged arginine side chains of the albumin molecule. The results are discussed in terms of the fibre-matrix hypothesis of capillary permeability and in terms of Brown's (1976) theory for the structure of albumin.
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PMID:The effects of native and modified bovine serum albumin on the permeability of frog mesenteric capillaries. 392 91

The free energy of the binding reaction between EcoRI restriction endonuclease and a specific cognate dodecadeoxynucleotide (d(CGCGAATTCGCG)) has contributions from both electrostatic and nonelectrostatic components. These contributions were dissected by measuring the effects of varying salt concentration on the equilibrium binding constant and applying the thermodynamic analyses of Record et al. (Record, M. T., Jr., Lohman, T. M., and deHaseth, P. L. (1976) J. Mol. Biol. 107, 145-158). Endonuclease mutation S187 (Arg 187 to Ser) (Greene, P. J., Gupta, M., Boyer, H. W., Brown, W. E., and Rosenberg, J. M. (1981) J. Biol. Chem. 256, 2143-2153) did not significantly affect the nonelectrostatic component but did perturb the electrostatic contribution to the binding energy (we are numbering the amino acid residues according to the DNA sequence). The former was determined by extrapolating the linear portion of the salt dependence curve (0.125 to 0.25 M KCl) to 1 M ionic strength, with the same result for both wild type and S187 endonucleases at both pH 6.0 and 7.4 (-8.5 +/- 1.5 kcal/mol or greater than 50% of the total binding free energy). The slopes of these same curves yield estimates of eight ionic interactions between wild type endonuclease and the DNA at both pH values. By contrast, binding of EcoRI-S187 to dodecanucleotide involves six charge-charge interactions at pH 6.0. Only two ionic interactions are observed at pH 7.4. This was unexpected since gel permeation chromatography demonstrated that the recognition complex for both wild type and S187 proteins contains an enzyme dimer and a DNA duplex. EcoRI-S187 endonuclease retains wild type DNA sequence specificity, and the rate of the phosphodiester hydrolysis step is also unchanged. Thus, electrostatic interactions are functionally separable from sequence recognition and strand cleavage. Our results also establish that arginine 187 plays a key role in the electrostatic function and suggest that it might be located at the DNA-protein interface. The disproportionate loss of ion pairs at pH 7.4 can be rationalized by a model which suggests that six conformationally mobile ionic groups on the protein act in a coordinated manner during the interaction with DNA.
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PMID:Coordinate ion pair formation between EcoRI endonuclease and DNA. 631 32

Transpositional mutagenesis of the mer operon of the IncFII plasmid, R100, has revealed a second, trans-acting positive regulatory function. Mutants in this function do not synthesize any of the three small mer operon peptides and have no inducible Hg(II) uptake activity. This second regulatory function is part of complementation group B and so depends upon the activity of the previously described trans-acting positive regulatory function merR. All mutants in this new function map in the amino-terminal 20 kDal of the Hg(II) reductase, suggesting either that this enzyme is also a regulatory protein or that there is a distinct protein whose reading frame is superimposed on that of the Hg(II) reductase. While we have only seen the five previously described mer operon peptides of 69, 66, 15.1, 14 and 12 (13) kDal encoded in minicells by single-copy plasmids, we have observed two new HgCl2-inducible polypeptides of approx. 20 kDal in minicells carrying a multicopy derivative of the mer operon of R100. Sequence data for the Hg(II) reductase region of the related mer operon of the transposon, Tn501 [Brown, N.L., Ford, S.J., Pridmore, R.D. and Fritzinger, D.C., Biochemistry 22 (1983) 4089-4095], shows a second reading frame very rich in cysteine and arginine which overlaps the amino-terminal 20 kDal of the Hg(II) reductase structural gene. We believe that this reading frame is the structural gene for this new regulatory function and propose the name merC (for control).
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PMID:A second positive regulatory function in the mer (mercury resistance) operon. 631 37

Five unique phycoerythrobilin (PEB) peptides were prepared from Porphyridium cruentum B-phycoerythrin by a combination of tryptic and thermolytic digestion without alteration in the spectroscopic properties of the bilin (Lundell, D.J., Glazer, A.N., DeLange, R.J., and Brown, D.M. (1984) J. Biol. Chem. 259, 5472-5480). alpha-1 Cys(PEB)-Tyr-Arg alpha-2 Leu-Cys(PEB)-Val-Pro-Arg beta-1 Met-Ala-Ala-Cys(PEB)-Leu-Arg beta-2T Phe-Ala-Ala-Gly-Asp-Cys(PEB)-Thr-Ser (Formula: see text) where alpha and beta refer to the subunits from which the peptides were derived High resolution 1H NMR analysis of peptides alpha-2, beta-1, and beta-2T combined with earlier studies of peptide alpha-1 (Schoenleber, R.W., Leung, S.-L., Lundell, D.J., Glazer, A.N., and Rapoport, H. (1983) J. Am. Chem. Soc. 105, 4072-4076) has provided proof that all of the singly linked PEB peptides contain a thioether bond to the 3' position of ring A, and strong evidence in support of a trans-dihydro ring A in each of these chromopeptides. The circular dichroism spectra of the four singly linked PEB peptides show that the configuration at C-16 is R in each instance. The present study coupled with previously reported results on peptide beta-3T (Schoenleber, R.W., Lundell, D.J., Glazer, A.N., Rapoport, H. (1984) J. Biol. Chem. 259, 5481-5484 provides the first comprehensive analysis of the structure of all the polypeptide-linked prosthetic groups on the alpha and beta subunits of B-phycoerythrin.
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PMID:Bilin attachment sites in the alpha and beta subunits of B-phycoerythrin. Structural studies on the singly linked phycoerythrobilins. 671 55

Allophycocyanin from Nostoc sp. phycobilisomes was separated into four spectrally distinct components designated allophycocyanin I, B, II, and III by adsorption chromatography on brushite columns. Allophycocyanins I and B had red-shifted fluorescence emission maxima, and on this basis, may function in transfer of excitation energy from phycobilisomes to chlorophyll a. Allophycyanins II and III, which together comprise 70% of the total allophycocyanin, have absorption maxima at 648 nm and 650 nm, respectively, and probably transfer excitation energy from phycocyanin to allophycocyanins I and B, in addition to serving a structural function. Allophycocyanin I was resolved into alpha, beta, and gamma subunits with apparent molecular weights of 18,000, 17,000, and 35,000, respectively, whereas allophycocyanin B was resolved into two subunits with apparent molecular weights of 16,100 and 15,300, using a modified Weber and Osborn gel electrophoresis system (Brown, A. S., and Troxler, R. F. (1977) Biochem. J. 163, 571-581). In the same gel system, allophycocyanins II and III were each resolved into alpha and beta subunits with apparent molecular weights of 18,000 and 17,000, respectively. The subunits of allophycocyanins I, II, and III were isolated by gel filtration and ion exchange chromatography and the amino acid compositions determined. Automated sequence analysis demonstrated that the first 30 amino acids at the NH2 terminus of alpha subunits, and the beta subunits, of allophycocyanins I to III were identical. alpha Subunits: Ser-Ile-Val-Thr-Lys-Ser-Ile-Val-Asn-Ala-Asp-Ala-Glu-Ala-Arg-Tyr-Leu-Ser-Pro-Gly -Glu-Leu-Asp-Arg-Ile-Lys-Ser-Phe-Val-Thr- beta Subunits: Ala-Gln-Asp-Ala-Ile-Thr-Ala-Val-Ile-Asn-Ala-Ala-Asp-Val-Gln-Gly-Lys-Tyr-Leu-Asp-Ala-Thr-Ala-Leu-Ser-Lys-Leu-Lys-Ala-Tyr- The gamma subunit of allophycocyanin I and both subunits of allophycocyanin B appeared to be blocked at the NH2 terminus, suggesting that the allophycocyanin B subunits may be different gene products than those of allophycocyanins I to III, or if the same, the subunits of allophycocyanin B undergo proteolytic modification after initial synthesis.
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PMID:Allophycocyanin from Nostoc sp. phycobilisomes. Properties and amino acid sequence at the NH2 terminus of the alpha and beta subunits of allophycocyanins I, II, and III. 741 Apr 30

Recent data has suggested a role for nitric oxide (NO) both in the induction of immunity and as an effector of tissue injury in experimental models of inflammation. In this study, we have tested the efficacy of two inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG), to modify the autoimmune leucocytoclastic necrotizing vasculitis which develops following the administration of mercuric chloride (HgCl2) to the Brown Norway rat. Neither agent affected the induction of autoimmunity as judged by plasma IgE titres or the degree of tissue neutrophil infiltration; however, L-NMMA did significantly attenuate tissue injury scores. We conclude that inhibition of NO synthase does not influence the induction of autoimmunity by HgCl2, but that NO does contribute to the development of tissue injury in this experimental model.
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PMID:Nitric oxide contributes to tissue injury in mercuric chloride-induced autoimmunity. 750 30


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