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)

T4-binding globulin (TBG), a 54-kilodalton glycoprotein, is the major thyroid hormone transport protein in man. The exact nature of the mutations causing X chromosome-linked TBG deficiency, which affect about 1 in 2,500 newborn males, is unknown. Here we report the sequence of a unique variant TBG (TBG-Gary) encoding a protein with severely impaired T4 binding as well as decreased stability at 37 C, resulting in its rapid in vivo denaturation. A single nucleotide substitution in the codon for residue 96 of the mature protein replaces isoleucine with asparagine; this replacement creates an additional site for N-linked glycosylation. The anodal shift of TBG-Gary on isoelectric focusing gel electrophoresis suggests that this new site is likely glycosylated. Since glycosylated is required for TBG to assume its correct tertiary structure, but is not subsequently necessary for maintenance of the biological properties or stability of the molecule, we believe that the likely presence of additional carbohydrate probably affects a higher order structure of the molecule and is thus responsible for the reduced stability and hormone binding activity of TBG-Gary (TBGASN-96).
Mol Endocrinol 1989 Mar
PMID:A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule. 250 69

It has previously been shown that spollAC561, a mutation that diminishes the incidence of sporulation by more than six orders of magnitude, alters the residue at position 13 of the helix-turn-helix region of the sporulation-specific sigma factor encoded by spollAC from valine to methionine (Yudkin, 1987b). We have now found that four spontaneous revertants, which sporulate at an incidence of 30-60%, all contain transitions within the codon that was altered by spo-561. The mutant methionine is replaced by isoleucine in two revertants, and by threonine in the other two.
Mol Microbiol 1989 Feb
PMID:Mutations that alter the helix-turn-helix region of the spollAC protein: a Bacillus subtilis sporulation-specific sigma factor. 250 77

Eucaryotic initiation factor 4A (eIF-4A) is a member of a family of proteins believed to be involved in the ATP-dependent melting of RNA secondary structure. These proteins contain a derivative of the consensus ATP-binding site AXXGXGKT. To assess the importance of the consensus amino acid sequence in eIF-4A for ATP binding, we mutated the consensus amino-proximal glycine and lysine to isoleucine and asparagine, respectively. The effect of the mutations was examined by UV-induced cross-linking of [alpha-32P]dATP to eIF-4A. Mutation of the lysine residue (but not of the glycine residue) resulted in the loss of [alpha-32P]dATP cross-linking to eIF-4A, suggesting that the lysine is an important determinant in ATP binding to eIF-4A.
Mol Cell Biol 1989 Sep
PMID:A lysine substitution in the ATP-binding site of eucaryotic initiation factor 4A abrogates nucleotide-binding activity. 250 40

In the presence of retinoic acid (RA), cultured F9 murine teratocarcinoma stem cells differentiate into nontumorigenic cells resembling the extraembryonic endoderm of the early mouse embryo. By differential hybridization screening of an F9 cell cDNA library, we isolated a 1,745-nucleotide cDNA for a gene, REX-1 (for reduced expression), whose steady-state mRNA level began to decline in F9 cells in monolayer culture within 12 h after the addition of RA. By 48 to 96 h after RA treatment of F9 cells in monolayer culture, the REX-1 steady-state mRNA level was more than sevenfold lower than the level in undifferentiated F9 stem cells. The REX-1 mRNA decrease did not result from the reduction in cell growth rate associated with the differentiation process, since the REX-1 mRNA level did not decline in F9 cells that were partially growth arrested after 48 h of isoleucine deprivation. The RA-associated REX-1 mRNA decrease resulted primarily from a reduction in the transcription rate of the REX-1 gene in the presence of RA. In contrast to results in F9 cells, we have been unable thus far to detect REX-1 mRNA in day 7.5 to 12.5 mouse embryo RNA samples or in the P19 teratocarcinoma stem cell line. The putative REX-1 protein identified by DNA sequence analysis contains four repeats of the zinc finger nucleic acid-binding motif and a potential acidic activator domain, suggesting that REX-1 encodes a regulatory protein. The REX-1 gene is not identical to the previously reported murine genes that encode zinc finger-containing proteins.
Mol Cell Biol 1989 Dec
PMID:Expression of REX-1, a gene containing zinc finger motifs, is rapidly reduced by retinoic acid in F9 teratocarcinoma cells. 251 39

The reassignment of codon AUA from isoleucine to methionine during mitochondrial evolution may be explained by the codon reassignment (capture) hypothesis without assuming direct replacement of isoleucine by methionine in mitochondrial proteins. According to this hypothesis, codon AUA would have disappeared from the reading frames of messenger RNA. AUA codons would have mutated mainly to AUU isoleucine codons because of constraints resulting from elimination of tRNA Ile with anticodon *CAU (in which *C is lysidine). Later, tRNA Met (CAU) would have undergone structural changes enabling it to pair with both AUG and AUA. AUA codons, formed by mutations of other codons, including AUG, would have reappeared and would have been translated as methionine.
J Mol Evol 1989 Nov
PMID:Evolution of the mitochondrial genetic code. II. Reassignment of codon AUA from isoleucine to methionine. 251 89

1. We carried out investigations on specific atrial natriuretic peptide (ANP) and angiotensin II (ANG) binding sites in capillaries isolated from the cerebral cortex of spontaneously hypertensive rats (SHR), an animal model of human essential hypertension, and also from Wistar Kyoto rats (WKY). 2. In an equilibrium binding study done in the presence of increasing concentrations of the radiolabeled ligands, the binding of 125I-rat alpha-ANP (1-28) [ANF-(99-126)] (125I-rANP) and 125I-ANG (5-L-isoleucine) (125I-ANG) to the cerebral capillaries was single and of a high affinity. 3. The maximum binding capacity (Bmax) and dissociation constant (Kd) in the 125I-rANP binding of 20-week-old, hypertensive SHR was significantly lower than in age-matched, normotensive WKY. Conversely, a significant increase in the Bmax of 125I-ANG binding of adult SHR was observed, with a significant decrease in the Kd. 4. There was no differences in the Bmax of 125I-rANP and 125I-ANG binding between 4-week-old, prehypertensive SHR and age-matched WKY. However, there was a significant decrease in the Kd of 125I-rANP binding of SHR. 5. As a dramatic change in the binding kinetics of 125I-rANP and 125I-ANG was noted in the cerebral capillaries of adult sustained-hypertensive SHR, the possibility that ANP and ANG play a role in the etiology of dysfunction of the blood-brain barrier complicated with hypertension, by interacting with specific receptors, would have to be considered.
Cell Mol Neurobiol 1989 Jun
PMID:Atrial natriuretic peptide and angiotensin II binding sites in cerebral capillaries of spontaneously hypertensive rats. 252 58

Native intact bovine PTH was studied by proton nuclear magnetic resonance (NMR) techniques, at pH 3.5 and pH 6.3. The 1H-NMR spectra had good resolution and many multiplet structures were observed. Assignment of the NMR resonances corresponding to specific amino acids was approached using 1H chemical shifts, coupling constants, and pH dependence in the one-dimensional spectra and the 1H-1H connectivities revealed in two-dimensional homonuclear correlated spectroscopy (COSY) experiments. All the aromatic proton resonances were assigned. Two histidine residues had lower pK than the other two. The methyl groups of two residues were moved significantly downfield: using COSY and two-dimensional nuclear Overhauser enhancement spectroscopy (NOESY) correlations, these were assigned to an alanine residue close to both Trp-23 and Tyr-43, and a valine residue in close spatial proximity to Trp-23. The NOESY spectrum also showed cross-peaks between the residues of the upfield valine-leucine-isoleucine methyl envelope. Many of the H alpha protons moved upfield as the pH was increased. These results indicate that intact native PTH exists in a preferred conformation in solution at pH 6.5. Our studies have provided new information on the three-dimensional spatial proximity of several amino acids along the polypeptide chain. The observed interactions are consistent with the currently accepted model suggesting that the hormone has two separate structural domains associated with the amino- and carboxy-terminal regions of the molecule respectively. The potential implications of this model for the expression of biological activity are discussed.
Mol Endocrinol 1989 Apr
PMID:Proton nuclear magnetic resonance studies of intact native bovine parathyroid hormone. 254 81

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, is subject to regulation by the cAMP as well as the calcium and cGMP second messenger systems. Treatment of intact rat PC12 cells with neuropeptides including secretin and vasoactive intestinal polypeptide (VIP) stimulated tyrosine hydroxylase activity 2 to 3-fold in vitro. Secretin (EC50 = 10 nM) was about 3 orders of magnitude more potent than VIP (EC50 = 3 microM). A combination of several protease inhibitors failed to enhance the potency of either peptide. Other members of the secretin family including glucagon and peptide histidine isoleucine (PHI) stimulated tyrosine hydroxylase activity to a lesser extent. Somatostatin, which is not homologous to secretin, was ineffective. The maximal response of tyrosine hydroxylase activation to 1 microM secretin occurred within 6-15 sec. Secretin, VIP, and forskolin also enhanced tyrosine hydroxylase activity (3,4-dihydroxyphenylalanine production) in intact cells, as determined by high performance liquid chromatography and electrochemical detection. Secretin, VIP, PHI, and glucagon increased the levels of cAMP in PC12 cells more than 10-fold, as determined by radioimmunoassay. We also demonstrated that cAMP is released from the cells into the incubation medium following secretin treatment. Secretin and VIP treatment also enhanced the activity of cAMP-dependent protein kinase in a concentration-dependent fashion, as measured subsequently in vitro. Based on the greater potency of secretin in comparison with VIP, PHI, and glucagon, we suggest that the PC12 cells contain a secretin-preferring receptor that increases cAMP levels and brings about an activation of tyrosine hydroxylase activity through the stimulation of cAMP-dependent protein kinase.
Mol Pharmacol 1989 Dec
PMID:Regulation of tyrosine hydroxylase activity in rat PC12 cells by neuropeptides of the secretin family. 257 21

Extrachromosomal mutants resistant to antimycin, from the yeast Kluyveromyces lactis, have been isolated, genetically characterized, and assigned to two specific genetic loci (Brunner et al., 1987). In the present work the cytochrome b nucleotide sequence from six of these mutants was determined. Five mutants had single point mutations, corresponding to transversions. In one mutant, a six-base-pair deletion, beginning at nucleotide 689, was observed. The amino acid sequence derived from the coding strand showed that, in three independent antimycin-resistant mutants, a change of asparagine 31 into lysine took place (two of these mutants are also resistant to diuron). Two other mutants showed a change from lysine 228 into isoleucine (or methionine). Leucine 230, isoleucine 231, and threonine 232, were lost in the deletion mutant and were replaced by serine.
Mol Microbiol 1989 Nov
PMID:Mitochondrial cytochrome b genes with a six-nucleotide deletion or single-nucleotide substitutions confer resistance to antimycin A in the yeast Kluyveromyces lactis. 261 56

The ilvIH operon of Escherichia coli encodes acetohydroxyacid synthase III, an isoenzyme involved in branched-chain amino acid biosynthesis. Transcription of the ilvIH operon is repressed by growing cells in the presence of leucine (C.H. Squires, M. DeFelice, S.R. Wessler, and J.M. Calvo, J. Bacteriol. 147:797-804, 1981). A protein in crude extracts of E. coli, termed the ilvIH-binding (IHB) protein, bound specifically in vitro to DNA upstream of the ilvIH operon. The binding protein, partially purified by Polymin precipitation, gel filtration, and phosphocellulose chromatography, has a native molecular weight of 43,000 and is composed of two subunits of identical size. As determined by protection against lambda exonuclease and DNase I, the protein binds within a region -190 to -260 relative to the start point of transcription. In addition, the IHB protein binds to a site between positions -100 and -40. The following evidence suggests that binding of this protein to the region upstream of ilvIH is related to the regulation of this operon by leucine. Binding of the IHB protein to the ilvIH regulatory region in vitro was reduced by leucine but not by isoleucine, valine, or threonine. In a mutant strain isolated by M.V. Ursini, P. Arcari, and M. DeFelice (Mol. Gen. Genet. 181:491-496, 1981), transcription was not repressed by leucine. A protein in extracts of this mutant strain bound to the ilvIH regulatory region, but the complex migrated through agarose gels with a mobility different from that of the complex formed by wild-type protein. Furthermore, a concentration of leucine that substantially reduced binding of the wild-type to DNA did not affect binding of the protein from the mutant strain. A simple model consistent with these findings is that transcription from the ilvIH promoter is stimulated by binding the IHB protein to one or more sites upstream of the promoter and that leucine interferes with this binding.
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PMID:A protein that binds to the regulatory region of the Escherichia coli ilvIH operon. 264 91


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