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

Previous calculations of electrostatic interactions in the rhinovirus capsid have identified a subset of histidine residues, paired with lysine or arginine, that may be involved in pH-induced conformational changes related to viral uncoating. Further calculations with the finite difference method, accounting for the dielectric environment of the ionizable groups, suggest that charge burial in the crystal conformation will prevent protonation of these histidine residues in the pentamer-pentamer interface. Calculations with a modelled pentamer-pentamer interface in which three beta-strands are removed recover mildly acidic pKa values for the histidines. These results are discussed in the context of the structural interactions of these three beta-strands, which form a beta-sheet extension from the rest of the capsid, and with regard to the conformation of the homologous beta-sheet extension in poliovirus, which also possesses homologous histidine-lysine/arginine pairs. A model is developed in which the structural stability of the beta-sheet extension is related to the difference in acid stability of rhinovirus and poliovirus. It is suggested that, for poliovirus prior to cell receptor binding, the beta-sheet extension is stable at pH 3, the pentamer-pentamer interface histidines remain buried, and the virus is acid-stable. Cell receptor binding of poliovirus destabilizes the beta-sheet extension and the acid lability that is proposed to result could be involved in viral uncoating. For rhinovirus it is suggested that the observed conformational change in the absence of cell receptor binding involves a further acidic pH-activated process or conformational fluctuations that rearrange the beta-sheet extension and expose the pentamer-pentamer interface histidine residues to the acidic medium. Sequence analysis and electrostatics calculations reveal an aspartic acid in the beta-sheet extension that may have different pKa values in rhinovirus and poliovirus.
J Mol Biol 1992 Jan 05
PMID:Model for the differential stabilities of rhinovirus and poliovirus to mild acidic pH, based on electrostatics calculations. 130 85

The heterodimer, human chorionic gonadotrophin (hCG), contains an alpha subunit that is common to the glycoprotein hormones and a hormone-specific beta subunit. A comparison of all known beta amino acid sequences shows that an aspartic acid at position 99 (with the numbering scheme for hCG-beta) is one of the seven non-Cys invariant residues. Using site-directed mutagenesis we have replaced hCG-beta Asp99 with Arg. Chinese hamster ovary cells, containing a stably integrated gene for bovine alpha subunit, were transiently transfected with plasmids containing wild-type and mutant hCG-beta cDNAs. The Arg99 beta mutant associated with the alpha subunit, but the resulting heterodimer failed to enhance intracellular cyclic AMP production in a gonadotrophin-responsive transformed murine Leydig cell line. Thus, a single amino acid residue replacement in this glycosylated heterodimer containing 237 amino acid residues is sufficient to abolish activity.
J Mol Endocrinol 1992 Feb
PMID:A single amino acid residue replacement in the beta subunit of human chorionic gonadotrophin results in the loss of biological activity. 131 31

The cytochrome c oxidase subunit I (COI) gene sequences from planarian (Dugesia japonica) DNA, most probably of mitochondrial origin, are heterogeneous. Taking advantage of the heterogeneity that occurs primarily in silent sites of the COI DNA sequences, amino acid assignments of several codons have been deduced as nonuniversal: UGA = Trp, AAA = Asp, and AGR (R: A or G) = Ser. In addition, UAA, a stop codon in the universal genetic code, is tentatively assumed to be a tyrosine codon, because three of the sequences examined have UAA at the well-conserved tyrosine site of UAY (Y: U or C) in other planarian sequences as well as in the mitochondria of human, Xenopus, sea urchin, Drosophila, Trypanosoma, and Saccharomyces cerevisiae. AUA would most probably be an isoleucine codon in these mitochondria, whereas it is a methionine codon in the majority of nonplant mitochondria.
J Mol Evol 1992 Apr
PMID:Planarian mitochondria. II. The unique genetic code as deduced from cytochrome c oxidase subunit I gene sequences. 131 9

HeLa cells attach to a variety of substrata but spread only on collagen or gelatin. Spreading is dependent on collagen-receptor upregulation, clustering, and binding to the cytoskeleton. This study examines whether second messengers are involved in initiating the spreading process on gelatin. The levels of cytosolic free calcium ([Ca++]i), cAMP, and cytoplasmic pH (pHi) do not change during cell attachment and spreading. However, a basal level of [Ca++]i and an alkaline pH(i) are required for spreading. There is an activation of protein kinase C (PKC) and a release of arachidonic acid (AA) on attachment and before cell spreading. Inhibition of PKC does not block cell spreading, indicating that PKC activation is not essential for spreading. Inhibition of phospholipase A2 blocks cell spreading, whereas addition of exogeneous AA overcomes this inhibitory effect. Among AA metabolic pathways, inhibitors of lipoxygenase (LOX) block cell spreading, suggesting that a LOX product(s) formed from AA initiates spreading. Clustering receptors for collagen with polyclonal antibodies, or with anti-collagen-receptor antigen-binding fragments (Fab) in combination with a secondary antibody, induce AA release. Also, AA is released when cells attach to either immobilized gelatin or immobilized Arg-Gly-Asp (RGD) peptide. Thus, AA is released whenever receptor clustering is observed. Receptor occupancy is not sufficient to release AA; when cells are treated with gelatin or RGD peptide in solution or anti-collagen-receptor Fab fragments without secondary antibody, conditions where receptor clustering is not observed, AA is not released. Thus, a LOX metabolite(s) of AA formed by collagen-receptor clustering is a second messenger(s) that initiates HeLa cell spreading. LOX inhibitors also block the spreading of bovine aortic endothelial cells, chicken embryo fibroblasts, and CV-1 fibroblasts on gelatin or fibronectin, indicating that other cells might use the same second messenger system in initiating cell-substratum adhesion.
Mol Biol Cell 1992 May
PMID:Spreading of HeLa cells on a collagen substratum requires a second messenger formed by the lipoxygenase metabolism of arachidonic acid released by collagen receptor clustering. 131 41

Thirteen 4,5-epoxymorphinan mu agonists with established analgesic action were docked into an Asp-Lys-His-Phe pseudoreceptor complex under a range of distance-dependent dielectric conditions. The number of compounds with potential energies of the docked complexes that agreed in rank order with corresponding analgesic potencies was determined for each condition. Two dielectric conditions, n-decane (1.991) and ethanol (24.3), enabled the greatest number of compounds to relate to their pseudoreceptors with each having 9 and 8 successes respectively. Both of these conditions demonstrated unique influences on the types of structures that were successfully docked. For example, the morphine stereoisomer alpha-isomorphine, the geometric isomer B/C trans-morphine, and the 8-position-substituted gamma-isomorphine were successes in the n-decane condition, whereas the ethanol condition produced the substituted codeine derivatives dihydrocodeinone and dihydroxycodeinone. These findings emphasize the importance of dielectric influence when developing force-field modeled quantitative structure-activity relationships for a closely related homologous series.
J Comput Aided Mol Des 1992 Apr
PMID:A pseudoreceptor docking study of 4,5-alpha-epoxymorphinans with a range of dielectric constants. 132 Jun 64

125I-Endothelin (ET)-1 and 125I-ET-3 displayed specific, saturable, and high affinity binding to membranes prepared from rat kidney cortex. Saturation binding experiments using 125I-ET-1 and 125I-ET-3 revealed that 125I-ET-3 binding sites were 40-50% less abundant than 125I-ET-1 binding sites. The dissociation constants (Kd) and maximum binding (Bmax) for 125I-ET-1 and 125I-ET-3 with these membranes were 218 +/- 23 pM and 275 +/- 20 fmol/mg of protein and 207 +/- 19 pM and 113 +/- 17 fmol/mg of protein, respectively. In the presence of 10 nM sarafotoxin 6c, a selective agonist for ETb receptors, 125I-ET-1 binding was decreased by 45-50% and 125I-ET-3 binding was totally abolished, suggesting that approximately 40-50% of kidney cortex ET receptors are of the ETB subtype and that 125I-ET-1 binds to both ETA and ETB receptors with the same high affinity, whereas 125I-ET-3 binds to only ETB receptors with high affinity. In addition, in the presence of BQ123 [cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu)], a selective antagonist for ETA receptors, 125I-ET-1 binding was decreased by 50%, whereas 125I-ET-3 binding was unaffected. Our results strongly suggest that rat kidney cortex contains ETA and ETB receptors in a 50:50 ratio and that sarafotoxin 6c and BQ123 are valuable tools in identifying the subtypes of ET receptors in various tissues.
Mol Pharmacol 1992 Aug
PMID:Identification of endothelin receptor subtypes in rat kidney cortex using subtype-selective ligands. 132 32

c-jun is a member of the family of immediate-early genes whose expression is induced by factors such as serum stimulation, phorbol ester, and differentiation signals. Here we show that increased Jun synthesis after serum stimulation is accompanied by a concomitant increase in phosphorylation. Several serine-threonine kinases were evaluated for their ability to phosphorylate Jun in vitro. p34cdc2, protein kinase C, casein kinase II, and pp44mapk phosphorylated Jun efficiently, whereas cyclic AMP-dependent protein kinase and glycogen synthase kinase III did not. The sites phosphorylated by p34cdc2 were similar to those phosphorylated in vivo after serum induction. The major sites of phosphorylation were mapped to serines 63, 73, and 246. Phosphorylation of full-length Jun with several kinases did not affect the DNA-binding activity of Jun homodimers or Fos-Jun heterodimers. Comparison of the DNA binding and in vitro transcription properties of wild-type and mutated proteins containing either alanine or aspartic acid residues in place of Ser-63, -73, and -246 revealed only minor differences among homodimeric complexes and no differences among Fos-Jun heterodimers. Thus, phosphorylation of Jun did not produce a significant change in dimerization, DNA-binding, or in vitro transcription activity. The regulatory role of phosphorylation in the modulation of Jun function is likely to be considerably more complex than previously suggested.
Mol Cell Biol 1992 Oct
PMID:Jun is phosphorylated by several protein kinases at the same sites that are modified in serum-stimulated fibroblasts. 132 60

A three-dimensional model of the serotonin (5-hydroxytrytamine; 5-HT) 5-HT2 receptor was constructed from the amino acid sequence by molecular graphics techniques, molecular mechanics energy calculations and molecular dynamics simulations. The receptor model has 7 alpha helical segments which form a membrane-spanning duct with a putative ligand binding site. Most of the synaptic domains and the ligand binding site were surrounded by negative electrostatic potentials, suggesting that positively charged ligands are attracted to the receptor by electrostatic forces. The cytoplasmic domains, except the C-terminal tail, had mainly positive electrostatic potentials. The molecular dynamics of the receptor-ligand complex was examined in 100 ps simulations with 5-HT or ritanserin at a postulated binding site. During the simulations the helices moved from an initial circular arrangement into a more oval arrangement, and became slightly tilted relative to each other. The protonated ligands neutralized the negative electrostatic potentials around Asp 120 and Asp 155 in the central core of the receptor. 5-HT had only weak interactions with Asp 155 but strong interactions with Asp 120 during the simulations, with the amino group of 5-HT tightly bound to the carboxylic side chain of Asp 120. Ritanserin showed similarly strong interactions with Asp 120 and Asp 155 during the simulations.
Brain Res Mol Brain Res 1992 Jul
PMID:Molecular dynamics of serotonin and ritanserin interacting with the 5-HT2 receptor. 133 49

The neuroendocrine light yellow cells of Lymnaea stagnalis form two clusters of cells in the visceral and right parietal ganglion, respectively. These cells are endogenously bursting neurons whose activities are modified during egg-laying and feeding. Using gel permeation chromatography and reverse phase HPLC we have purified two highly related novel peptides from the light yellow cells. These peptides differ only in length, due to truncation of the amino-terminal aspartic acid residue, which causes a major shift in the charge of the molecule. We conclude that the longer peptide is the immediate precursor of the shorter form. Using whole mount immunocytochemistry, it was confirmed that the light yellow cells produce these peptides.
Brain Res Mol Brain Res 1992 Nov
PMID:Chemical characterization of a novel peptide from the neuroendocrine light yellow cells of Lymnaea stagnalis. 133 2

Aspartate-beta-semialdehyde dehydrogenase catalyzes the NADPH-mediated reductive dephosphorylation of beta-aspartylphosphate at a branch point in the biosynthesis of several amino acids. The enzyme from Escherichia coli has been crystallized by the vapor diffusion method from Tris buffer (pH 8.5) using polyethylene glycol 4000 as a precipitant. The crystals are orthorhombic and have the symmetry of space group P222(1), with unit cell dimensions of a = 177.8 A, b = 59.9 A, c = 118.65 A, and alpha = beta = gamma = 90 degrees. The dimensions and space group are indicative of two enzyme dimers (40 kDa per subunit) in the asymmetric unit. The crystals show strong diffraction, and a native data set has been collected to 2.5 A resolution.
J Mol Biol 1992 Nov 05
PMID:Crystallization and preliminary crystallographic analysis of aspartate-beta-semialdehyde dehydrogenase from Escherichia coli. 136 28


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