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)

With puromycin one can recognize when the synthesis of a given protein is dependent on amino acyl tRNA that is present in rate limiting amount. We demonstrate this use of puromycin by its interaction with another inhibitor, L-o-methylthreonine. L-o-methylthreonine lowers the Ile-tRNA concentration in the cell, thereby inhibiting synthesis of proteins containing isoleucine. In certain rabbits, the alpha hemoglobin chain has three isoleucyl residues and the beta chain none. L-o-methylthreonine thus inhibits alpha globin synthesis in intact reticulocytes from these rabbits. When puromycin and L-o-methylthreonine are used together, the two inhibitors synergize in inhibiting alpha globin synthesis. Hence, puromycin is a more effective inhibitor when the Ile-tRNA concentration is lowered. Cycloheximide and sodium fluoride have different modes of action from puromycin. Neither synergizes with L-o-methylthreonine; instead, the interaction is less than additive. We have found that beta chain synthesis in rabbit reticulocytes is more sensitive than alpha to inhibition by puromycin. This difference could reflect either differences in amino acid sequence or tRNA dependent limitations of beta chain elongation. The switch from fetal to adult hemoglobin in humans does not involve changes in limiting amino acyl tRNA because, for cord blood from infants of different developmental ages, the puromycin sensitivity of incorporation into gamma and beta chains remains constant.
Mol Cell Biochem 1978 Feb 24
PMID:Testing with puromycin and amino acyl tRNAs that limit the rate of peptide chain extension. 24 96

Previous studies from this laboratory have shown that the expression of globin genes during the dimethyl sulfoxide-induced differentiation of T3C12 Friend erythroleukemia cells in inhibited by dexamethasone and related glucocorticoids. The present report shows that dexamethasone exerts a similar effect on the accumulation of globin mRNA and hemoglobin in differentiating GM86 Friend cells, but that these cells are less sensitive to this hormone. The higher sensitivity of T3C12 cells has been correlated with the presence of 6 times as many cytoplasmic glucocorticoid receptors as in the GM86 cells. The receptors of T3C12 cells have been shown to have properties in common with glucocorticoid receptors found in other tissues. It is proposed that these receptors may be responsible for the steroid control of the globin genes in Friend cells.
Mol Cell Endocrinol 1979 Mar
PMID:Possible role of glucocorticoid receptors in globin gene expression in differentiating Friend cells. 28 65

It was shown that ferrocytochrome P450 forms a nonequilibrium state if ferrocytochrome P450 and its complexes are reduced in freezed water-glycerol solutions by thermolysed electrons, arising during gamma-radiolysis of the matrix at 77 degrees K. Unlike the equilibrium form of ferrocytochrome P450 with the heme iron at the high-spin state the reduced nonequilibrium form of the protein contains the heme iron at a low-spin state. The absorption spectrum of ferrocytochrome P450 in the nonequilibrium state is characterized by alpha and beta-bands at 562 and 534 nm, respectively, whereas the magnetic circular dichroism spectra exhibit type A effect at 562 nm. Upon temperature increasing the nonequilibrium state is relaxed to the equilibrium one. Type 1 substrates had practically no influence on the spectral characteristic of the nonequilibrium form of ferrocytochrome P450. Binding of type 2 substrates results in an essential decrease of the intensity ratio of the alpha- and beta-bands (A alpha/A beta) and is accompanied by a red-shift of the alpha-band and corresponding magnetic circular dichroism effect. It was shown that mercaptoethanol complex of hemoglobin, formed by reduction at 77 degrees K is spectrally similar to the nonequilibrium ferrocytochrome P450 complex with type 2 substrates. From analysis of experimental data one can conclude that (i) the ligand environment of heme iron in oxidased and reduced cytochrome P450 are different; (ii) the sixth axial ligand of the heme iron in the oxidised protein is probably a water molecule (OH-) attached by a hydrogen bond to the neighbouring histidine. It is assumed that a similar nonequilibrium form of cytochrome P450 can be formed in physiological conditions.
Mol Biol (Mosk)
PMID:[Absorption and magnetic circular dichroism spectra of hemoproteins in nonequilibrium states. V. Cytochrome P450 and its substrate complex]. 54 82

The genetic code may be used to formulate the nucleotide sequence of a messenger RNA from the known amino acid sequence of a protein. Unfortunately, the degeneracy of the code means that there will be ambiguity in the nucleotide assignments in a third or more of the positions. A simple procedure is given that utilizes the information of known genetic variants to reduce that ambiguity. Problems associated with silent polymorphism are treated. The human alpha and beta hemoglobins are used to exemplify the technique. A total of 68 nucleotides in the two sequences are thereby made less ambiguous. One reduction leads to a nucleotide inconsistent with the result of the recently published beta hemoglobin sequence.
J Mol Evol 1977 Nov 25
PMID:The restriction of codon ambiguity on the basis of known variants. 59 25

The paper deals with the action of: primaquine, epinephrine, adrenochrome, acetylphenylhydrazine and sulphanilamide on the autoxidation of the isolated chains from human hemoglobin and on the precipitation which follows. The effect of superoxide dismutase and catalase on the drug induced autoxidation allows the assessment of the possible role of O2 derivatives (notably superoxide or peroxide) in the overall reaction mechanism. It is also shown that primaquine and acetylphenylhydrazine enhance precipitation of the isolated oxidized chains, while epinephrine and adrenochrome display a small inhibitory effect on precipitation. These effects do not involve O2 radicals, but have presumably to be related to a destabilizing (or stabilizing) action of the drugs on the structure of the protein.
Mol Cell Biochem 1978 Feb 24
PMID:Effect of drugs on oxidation and precipitation of the isolated chains of human hemoglobin. 64 35

It has been recently demonstrated that some nitrosyl hemoglobin derivatives have different optical spectrum according to the nature of their quaternary structure (Cassoly, R. (1974) C. R. Seances Acad. Sci., Paris 278, 1417-1420; Salhany, J. M., Ogawa, S., and Shulman, R. G. (1974) Proc. Natl, Acad. Sci. U.S.A. 71, 3359-3362; Cassoly, R. (1975) J. Mol. Biol. 98, 581-595). This property has been used in order to detect the presence of asymmetrical hybrids alphaNObetaNOalpha'O2beta'O2 in a mixture of the two hemoglobins alpha2NObeta2NO and alpha2'O2beta2'O2. When one changes, by deoxygenation, the conformation of the hybrid, there is a characteristic modification in the optical spectrum of the nitrosyl subunits. Quantitative analysis of this phenomenon shows that asymmetrical alphaNObetaNOalphadeoxybetadeoxy and symmetrical alpha2NObeta2deoxy hybrids have distinct properties. The structure-linked optical transition is different in rate and amplitude; it is faster and larger for the asymmetrical molecule. Carbon monoxide binding kinetics performed in absence of phosphate have also indicated that the allosteric equilibrium is more displaced in favor of the T state for alphaNObetaNOalphadeoxybetadeoxy by comparison with the symmetrical deoxygenated intermediates.
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PMID:Use of nitric oxide as a probe for assessing the formation of asymmetrical hemoglobin hybrids. An attempted comparison between alphaNObetaNOalphadeoxybetadeoxy, alpha2NObeta2deoxy, and alpha2deoxybeta2NO hybrids. 64 91

The codons in four mammalian messenger RNAs (rabbit beta hemoglobin, rat pre-proinsulin, rat pre-growth hormone and human chorionic somatomammotropin) show a predominance of C and G in third nucleotide positions. The C:U ratio is about 2 to 1, and the G:A ratio is about 4 to 1. The possibility is discussed that this disproportionally resulted from DNA replicative errors that favor C.G pairs over A.T pairs, as found in the E. coli mut T strain. "Nearest neighbor" base pairs ("doublets") in the protein-coding regions of phiX174 and in four mammalian mRNAs have been compared. Mammalian mRNA has a low content of CpG in comparison with expectations from its C and G content.
J Mol Evol 1978 Jun 20
PMID:Codons and nearest-neighbor nucleotide pairs in mammalian messenger RNA. 67 60

Absorption and magnetic circular dichroism spectra of nonequilibrium states of hemoglobin and its derivatives formed by reduction oxidased forms of hemoproteins by thermalysed electrons at 77 degrees K were studied. Mixtures of low spin and high spin ferroforms were observed for nonequilibrium hemoglobin and its complexes with inosithexaphosphate and fluorine. The content of the high spin form increasing as follows: hemoglobin, complex with inosithexaphosphate, complex with fluorine. Only low spin forms were found for cyanide and azide complexes of hemoglobin reduced at low temperature. The spectral differences of nonequilibrium low spin ferroforms were supposed to be due to the presence of different ligands in the coordination sphere of the heme iron. The alpha-band splitting was observed for the nonequilibrium imidazole complex of hemoglobin. This effect was explained by a lowe-ring of the active centre's symmetry. The temperature relaxation of all nonequilibrium systems was investigated.
Mol Biol (Mosk)
PMID:[Absorption spectrum and magnetic circular dichroism of heme-containing proteins in nonequilibrium states. I. Hemoglobin and its derivatives]. 68 98

The concept of phylogenetic denseness bears critically on the accuracy of evolutionary pathways inferred from experimentally sequenced proteins isolated from extant species. In this paper I develop an objective measure, rho, of denseness to supplement previous intuitive concepts and which permits one to use this concept in comparing the quality of different evolutionary reconstructions. This measure is used to examine several published phylogenetic trees: insulin, alpha-hemoglobin, beta-hemoglobin, myoglobin, cytochrome c, and the parvalbumin family. The paper emphasizes 1) the importance of denseness in accurately estimating the number of nucleotide replacements which separate homologous sequences when this estimation is made by the method of parsimony, 2) the value of this concept in assessing the quality of those estimates, and 3) the use of this concept as a biologically practical heuristic method for identifying poorly studied regions in a phylogenetic tree, whether or not the tree was obtained by the parsimony method.
J Mol Evol 1978 Aug 02
PMID:A measure of the denseness of a phylogenetic network. 69 Oct 73

Determinations of carbon monoxide binding curves for hemoglobin from Brevoortia tyrannus under equilibrium and photostationary conditions show that in the light, the curve is shifted to the right and altered in shape. The Bohr effect is much less in the light. The kinetics of the transition between equilibrium and photostationary states has been examined. All of the results are satisfactorily described using the two-state model of Monod, J. Wyman, J., and Changeux, J.P. (1965) J. Mol. Biol. 12, 88-118 with the assumption that light produces an additive increase in the rate of dissociation of ligand from the R and T states.
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PMID:Carbon monoxide binding to a fish hemoglobin under photostationary conditions. 70 Dec 55


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