Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The complement components (C6, C7, C8 and C9) implicated in the lysis of target cells and the pore-forming, lytic protein from cytotoxic T-lymphocytes and NK-cells, perforin, contain an amino acid sequence which is highly homologous to a repeat unit identified in the LDL-receptor (Tschopp et al., 1986, Nature, 322, 831-834). The domain of the LDL-receptor, which is thought to interact with a positively charged segment of its ligands apoprotein B and E, is rich in cysteine residues and contains a cluster of negative charges. We show that the negatively charged molecules suramin and glycosaminoglycans, the positively charged peptides protamine and polylysine, all of which are known to abolish binding of LDL to its receptor (Goldstein et al., 1985, A. Rev. cell. Biol., 1, 1-39) inhibit the lytic activities of C6, C7, C8, C9 and perforin. Moreover, these negatively charged molecules are potent inhibitors of cytolytic T-lymphocyte-mediated lysis of target cells, suggesting a functionally crucial role for perforin in cell-mediated cytolysis. We propose that the negatively charged, cysteine-rich domain of these complement proteins and perforin interacts with an as yet unidentified positively charged segment of its ligand in a manner analogous to the LDL-LDL receptor interaction. Homologous cysteine-rich domains in functionally unrelated proteins may therefore be functionally conserved as ideal rigid interaction domains with the conserved cysteine residues as framework. Specificity of the domain for its ligand would be conferred by the non-conserved amino acid residues.
Mol Immunol 1987 Sep
PMID:Inhibition of the lytic activity of perforin (cytolysin) and of late complement components by proteoglycans. 349 87

The prediction of protein conformation by homology is being widely pursued using interactive computer graphics. However, there have been a limited number of energy minimization and/or molecular dynamics studies for such predictions. This paper reports one such study on alpha-lactalbumin, a system that can be tested as the X-ray crystal structure has recently been determined. The differences in structure of the Ca2+ binding loop reported for the holo-protein (Stuart et al., Nature, 324 [1986] 84-87) and that predicted for the apoprotein could be attributed to the presence or absence of the Ca2+ ion.
J Comput Aided Mol Des 1987 Apr
PMID:Modelling of alpha-lactalbumin from the known structure of hen egg white lysozyme using molecular dynamics. 350 84

Changes in cytochrome P-450 isoenzymes were studied in rat liver and in primary cultures of rat hepatocytes after treatment with compounds belonging to various classes of inducers, including phenobarbital (PB), beta-naphthoflavone (BNF), and clofibrate/clofibric acid (CLOF/CLOFA). The enzyme activity toward specific substrates was measured, and the presence of apoprotein of several P-450 isoenzymes was determined semiquantitatively by Western blotting. In untreated cultures the P-450 content and activities of 7-ethoxyresorufin O-deethylation (EROD) and aniline 4-hydroxylation (AH) declined with time at different rates. In cultures treated with BNF, the protein levels of isoenzyme P-450IA1 and P-450IA2 were elevated, as in vivo. This induction was reflected in a markedly increased EROD activity. CLOFA enhanced the AH and EROD activity in primary cultures at the same level as in vivo. The monooxygenase activity pentoxyresorufin O-depentylation (PROD) was stimulated by PB and CLOF in vivo, which correlated with the enhanced protein level of P-450IIB1/2. In contrast, the PROD activity was not induced when cultures were treated with PB or CLOFA, although we could detect apoprotein of P-450IIB1/2 by immunoblotting.
Mol Toxicol
PMID:Induction and activity of several isoenzymes of cytochrome P-450 in primary cultures of rat hepatocytes, in comparison with in vivo data. 350 91

We have previously shown that a lipoprotein fraction consisting of large cholesteryl ester-rich particles can be isolated from homogenates of human aortic plaques by gel exclusion chromatography. This fraction was recognized by a high-affinity binding site on mouse peritoneal macrophages (MPM) resulting in unregulated uptake, stimulation of cholesterol esterification, and massive accumulation of cholesteryl esters. In this report we have further characterized such a fraction, designated lipid-protein complex (LP), which can be isolated from the void volume fraction of a Bio-Gel A-150m column following chromatography of plaque extracts. LP possessed a mean cholesterol-to-protein ratio of 2.3; it was heterogeneous in size and structure as observed by electron microscopy after negative staining, and it stimulated cholesterol esterification in MPM in a linear fashion over a 48-hr time interval, suggesting that the binding site on MPM recognizing LP was not down-regulated by intracellular cholesterol content. This uptake resulted in the presence of oil red O-positive intracellular droplets and numerous vacuoles containing electron-dense structures, whereas MPM incubated without lipoprotein showed few vacuoles or lipid droplets. Using SDS-PAGE and immunoblot and dot-blot techniques, we found that the major proteins associated with LP were albumin and fibronectin, whereas apoB and apoE were present in lower amounts. These proteins may be responsible for opsonization of LP, making it recognizable to receptors on MPM and facilitating LP uptake by MPM. LP isolated from tissue extracts without homogenization had the same structural and functional characteristics, suggesting that homogenization per se was not responsible for creating a particle that was recognized by MPM. However, homogenization yielded two to three times more LP. MPM uptake of LP derived from lysed foam cells may represent one of the mechanisms by which fatty streak lesions may grow to larger atherosclerotic lesions.
Exp Mol Pathol 1987 Jun
PMID:Uptake by mouse peritoneal macrophages of large cholesteryl ester-rich particles isolated from human atherosclerotic lesions. 359 4

An intracisternal protein in the type II pneumocyte of the ferret, guinea pig, and mongrel dog was examined by light and electron microscopy and morphometry. The basic pattern of layering in this membrane-bound, ribosome-studded structure (cisternal body) was visualized in cross section as dense layers separated by approximately 0.1 micron with seven fine layers between. In all species the central fine band of the seven was occasionally more prominent than the other six. In the guinea pig the seven fine layers alternated in density from light to dark. The cisternal body of the dog was similar to that of the ferret, but was very much smaller and encountered infrequently. No function has been ascribed to this structure; however, its relation to lamellar bodies, the perinuclear membrane, and surfactant apoprotein is discussed.
J Ultrastruct Mol Struct Res
PMID:Intracisternal protein in the type II pneumocyte of the ferret, guinea pig, and mongrel dog. 361 44

Possible origins of the different metal co-ordination topologies in the recently determined structures of rat metallothionein-2 (MT2) in single crystals and rabbit MT2 in solution were investigated. A complete structure determination for rat MT2 in solution by nuclear magnetic resonance (n.m.r.) showed that the differences in the spatial structures cannot be attributed to the different primary structures of the two species. Comparison of [113Cd7]MT2 obtained by reconstitution of the apoprotein in vitro with preparations using a different procedure showed, moreover, that the metal co-ordination observed in solution by n.m.r. is not an artefact of the protein reconstitution. Solutions of high-pressure liquid chromatographically homogeneous biosynthetic preparations of [113Cd, Zn]MT2 were obtained from rat liver following injection of 113Cd into rats in vivo, without further metal exchange after protein isolation. They contain a mixture of several forms of MT2 with different relative metal compositions, giving rise to an increased number of 113Cd resonances. For the components of the four-metal cluster, the major one of these different forms exhibits patterns in the two-dimensional [1H, 113Cd]-correlated spectra that are indistinguishable from those of [113Cd7]MT2, thereby implying identity of cluster coordination and topology. These results are discussed with regard to continued investigations into the differences between the solution structure and crystal structure of MT2.
J Mol Biol 1987 Aug 05
PMID:Metal co-ordination in rat liver metallothionein-2 prepared with or without reconstitution of the metal clusters, and comparison with rabbit liver metallothionein-2. 368 73

A proton nuclear magnetic resonance study of the reaction of apohemoglobin A with both oxidized and reduced hemes reveals that at least two slowly interconverting species are initially formed, only one of which corresponds to the native proteins. Reconstitutions with isotope-labeled hemes reveal that the hyperfine-shift patterns for heme resonances in the metazido derivatives differ for the two species by interchange of heme environment characteristic of heme orientational disorder about the alpha, gamma-meso axis, as previously demonstrated for myoglobin [La Mar, G. N., Davis, N. L., Parish, D. W., & Smith, K. M. (1983) J. Mol. Biol. 168, 887-896]. Careful scrutiny of the 1H NMR spectrum of freshly prepared hemoglobin A (Hb A) reveals that characteristic resonances for the alternate heme orientation are present in both subunits, clearly demonstrating that "native" Hb A possesses an important structure heterogeneity. It is observed that this heterogeneity disappears with time for one subunit but remains unchanged in the other. This implies that a metastable disordered state in vivo involves the alpha subunit and an equilibrium disordered state both in vivo and in vitro is involved within the beta subunit. The presence of metastable disorder in fresh blood suggests an in vivo hemoglobin assembly from apoprotein and heme that is similar to the in vitro reconstitution process. The slow equilibration and known lifetimes for erythrocytes provide a rationalization for the presence of detectable metastable states. The implications of such heme disorder for Hb function are discussed.
 ...
PMID:1H NMR characterization of metastable and equilibrium heme orientational heterogeneity in reconstituted and native human hemoglobin. 405 68

The site responsible for the mercaptan (or borohydride)-stimulated DNA scission activity of neocarzinostatin chromophore (NCS-Chrom) is located in the central C12-subunit of the molecule. This has been determined by studies of the characteristic spectral properties of the chromophore and its reduction products and of the spectral changes induced by their interaction with its apoprotein (apo-NCS) and DNA. The UV-visible absorption, fluorescence, CD, and MCD spectral properties of the major nonprotein chromophoric component of neocarzinostatin (NCS-Chrom A) are assigned to its component substructures, the 2-hydroxy-5-methoxy-7-methyl-1-naphthoate, the five-membered cyclic carbonate ring (1,3-dioxolan-2-one), the 2,6-dideoxy-2-methylaminogalactose, and the incompletely defined C12-subunit which links the other three residues. Although the major source of its UV-visible absorption is the naphthoic acid residue (HNA-NCS), a significant absorption from approximately 260 to 330 nm is due to the presence of the highly unsaturated C12-subunit. The presence of the C12-subunit and, to a lesser extent, the cyclic carbonate reduces the intensity of the fluorescence emission of the fluorophore of NCS-Chrom A, the HAN-NCS subunit. The CD activity of NCS-Chrom A is also due to the presence of the C12-subunit. The MCD activity of NCS-Chrom A, however, is completely accounted accounted for by the naphthoic acid residue. A role for the C12-subunit in the binding of NCS-Chrom to DNA or apo-NCS is indicated by the resultant absorption hypochromicity in the region assigned to the C12-moiety. Limited modification of the C12-subunit (by mercaptan or borohydride) inactivates the chromophore for DNA strand scission, although both products still bind DNA. The naphthoic acid residue alone is not sufficient for binding to DNA. Therefore, the intercalation of the naphthoate residue between DNA base pairs requires the binding of NCS-Chrom to DNA probably via electrostatic interaction between the positively charged 2-methylamino group of the galactose residue and the negatively charged oxygens of the phosphate in the DNA backbone. The C12-unit is viewed as forming a short-lived reduction-activated species that, in the presence of oxygen, causes single-strand breaks in DNA. The cyclic carbonate residue is not required for in vitro DNA strand scission activity but affects its stability with respect to hydrolysis and reactivity with mercaptan. If DNA is absent the activated species decompose to inactive products, including a mercaptan (or hydrogen) addition product of the C12-subunit.
Mol Pharmacol 1983 Mar
PMID:Neocarzinostatin chromophore. Assignment of spectral properties and structural requirements for binding to DNA. 622 Feb 5

Crystals of three forms of human plasma apo-retinol-binding protein have been obtained using the procedure described for the holoprotein. The apoprotein was prepared by a novel method, which uses hydrophobic interaction and immobilized dye chromatography. The three forms were separated by fast protein liquid chromatography. All of the crystals are isomorphous and diffract to 2.5 A resolution. These crystals will be useful for studies of the mechanism of binding of retinol to its carrier using X-ray diffraction techniques.
J Mol Biol 1984 Sep 15
PMID:Crystallization of human plasma apo-retinol-binding protein. 654 4

p3phycoerythrin is the major phycobiliprotein of Rhodophyta and endows these algae with the characteristic color. R-phycoerythrin purified from red alga Calithamnion rubosom is composed of four dissimilar polypeptide subunits, alpha, beta, gamma, and delta. In calibrated SDS gel electrophoresis their molecular weights are 21 000, 21 600, 31 000 and 33 000 daltons, respectively. The stoichiometry of the subunits in the native protein is 9 alpha: 9 beta: 2 gamma: 1 delta. R-phycoerythrin carries two covalently linked apoprotein red tetrapyrrol pigments: phycoerythrobilin (PEB) and phycourobilin (PUB). Chemical and spectroscopic data show that alpha subunit carries solely two PEB chromophores, beta subunit--3 PEB and 1 PUB groups, gamma subunit--3 PEB and 2 PUB groups and delta subunit--1 or 2 PEB and 1 PUB groups. The chromophore and polypeptide structure of R-phycoerythrin is mostly composed of all known phycobiliproteins of red and blue-green algae.
Mol Biol (Mosk)
PMID:[Molecular organization and pigment composition of R-phycoerythrin from the red alga Callithamnion rubosum]. 671 17


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