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)

Influence of pH on absorbance and CD-spectra of DNA in PEG-containing water-salt solutions has been studied. The changes in the spectra appeared due to disturbance of the DNA secondary structure upon acidification of the medium proir to or after DNA compactization. If acidification preceeds DNA compactization an intense negative band in the CD spectrum inherent to the compact particles is observed at pH values 7-4. The intensity of the band decreases with an increase of the acidity. The size of the compact particles as evaluated from the dependence of the apparent optical density on the wavelength value remains unchanged (about 1200 A). If the solution is strongly acidified (pH 4.0-2.8) and a considerable disturbance in the DNA secondary structure takes place a negative band in the CD spectrum completely disappears. If one acidifies a solution containing preformed DNA compact particles a decrease of the intensity of the CD negative band starts at lower pH values (less than 2.8). This process is accompanied by an increase of the size of the particles. Acidic "denaturation" of DNA within the compact particles (pH approximately 2.5) is followed by a dissappearance of the CD negative band and a considerable increase of the particle size. The data obtained indicate that the specific arrangement of DNA strands manifested in a CD negative band depends on the defects in the DNA secondary structure.
Mol Biol (Mosk)
PMID:[The compact form of DNA in solution. IV. The effect of secondary structure defectiveness on the arrangement of double-chained DNA molecules into compact particles]. 0 1

Conformational states of fibrinogen and fibrin monomer were studied by methods of differential and solvent-perturbation spectrophotometry and ultraviolet fluorescence at about neutral pH (6.5) and in the region of lower pH, 3.2 to 4.0. To prevent repolymerization of fibrin monomer at pH 6.5, urea was added in a non-denaturing concentration of 1.7 M. In the acid region specified, the immediate environment of tyrosine and tryptophan residues was found to be more polar and the accessibility to perturbants higher than at pH 6.5. Much more drastic changes of the same type occurred at pH less than 3 when denaturation of the protein takes place. The conformation of fibrinogen altered progressively upon lowering pH from 4.0 to 3.2. This acidity increase, practically, did not influence the conformation of fibrin monomer. Thus the tolerance of the latter to the appearance of the new positively changed groups seems to be comparably high. The bulk of the conformational changes subsequent upon neutralization of an acid fibrin monomer solution proceeds at a higher rate than the activation transition, i.e. the acquirement of a state of polymerization readiness by fibrin monomer molecules.
Mol Biol (Mosk)
PMID:[Fibrinogen and fibrin monomer conformation changes dependent of pH magnitude]. 0 45

Concentration dependence of the equivalent conductance of isoionic DNA solutions has been studied at different temperatures. The limiting equivalent conductance (lambda infinity) at every temperature investigated has been obtained by extrapolation to the infinite dilution in Kohlraush's plots. At the same time in plots c lambda c versus 1/lambda c (lambda c is equivalent to conductance at the concentration c), corresponding to the linear form of Ostwald's dilution law, the straight lines were obtained. Both lambda infinity and acidity constants (K) have been determined from these plots. The values of lambda infinity by two methods are in well agreement. The average values of lambda infinity were used for energy activation of conductivity calculation, equal to 2,40 +/- 0,05 kcal/mole. The acidity constant of primary phosphoryl groups passes through a maximum near 33 degrees. Equivalent conductance of hydrogen ions calculated by neglecting of macroion's mobility and by using of potentiometric determined concentration (cH+) has been shown to increase with cH+. Unusual behavior of DNA in isoionic solutions is discussed.
Mol Biol (Mosk)
PMID:[Temperature dependence of conductance of isoionic DNA solutions. Determination of dissociation constants of primary phosphoryl groups]. 3 37

1. The effect of metiamide on gastric acidity in man has been studied. Solutions of hydrochloric acid or glucose were instilled into the stomach and the subsequent rates of gastric secretion and emptying, and the disappearance of acid within the stomach, were measured. 2. Metiamide inhibited the gastric secretory response to the instilled acid and glucose solutions but did not change the overall pattern of emptying of the instilled solutions. 3. During administration of metiamide, there was a net loss of acid from within the gastric lumen. The rate of disappearance of acid from the instilled acid solution was small and not sufficient in magnitude to account for the metiamide-evoked decrease in the concentration of acid secreted in response to pentagastrin. 4. We conclude that metiamide does not inhibit gastric secretion by altering the 'barrier' function of the gastric mucosa.
Clin Sci Mol Med 1975 Nov
PMID:Effects of metiamide on the human stomach. 110 45

The proton nuclear magnetic resonance spectrum of azurin from Alcaligenes denitrificans at pH 6.0 and 309 K is reported. Proton signals from all methionine and histidine residues (among them the copper ligands) have been assigned. The data have been used to study the pH behaviour of His35 and to establish the electron self-exchange rate of the protein. His35 appears to be protonated at pH less than 4.5, possibly after rupture of a salt bridge. No effects of this protonation on the tertiary structure around the copper site are observed, however, contrary to the case of Pseudomonas aeruginosa azurin. The electron self-exchange rate amounts to 4 x 10(5) M-1 S-1 at pH 6.7 and 297 K. The data support the conclusion that the electron self-exchange takes place by way of the hydrophobic surface patch around His117, and that His35 is not involved in this reaction. Oxidation of azurin increases the acidity of the freely titrating His32 and His83 by 0.07 and 0.25 pKa units, respectively. The data can be used to test the theory of electrostatic interactions in proteins. The optical extinction coefficient at 625 nm was experimentally determined and amounts to 4.8(+/- 0.1) x 10(3) M-1 cm-1.
J Mol Biol 1988 Mar 05
PMID:1H nuclear magnetic resonance study of the protonation behaviour of the histidine residues and the electron self-exchange reaction of azurin from Alcaligenes denitrificans. 283 76

Using model systems, we have studied the properties of a number of zinc-chelating agents which are known to cause diabetes in laboratory animals. The abilities to permeate membranes and to complex zinc inside liposomes with the release of protons are suggested as chemical properties that can enhance diabetogenicity. When such complexing agents are added to lipid vesicles at pH 6 containing entrapped zinc ions, they acidify the contents of these vesicles. We have demonstrated this effect by measuring intravesicular pH both with a fluorine-containing F NMR probe as well as with the fluorescent probe, quinine. For example, using quinine, we observed that 0.1 mM 8-hydroxyquinoline reduced the intravesicular pH of sonicated phospholipid vesicles containing entrapped Zn2+ (as sulfate) from pH 6.0 to 2.8. These diabetogenic chelating agents also solubilized zinc-insulin precipitates from unbuffered suspensions at pH 6.0. The solubilization results from the acidification of these suspensions. Dithizone and 8-hydroxyquinoline at 4 mM solubilized 97 and 42%, respectively, of the suspended insulin. We suggest that if such proton release occurs within the zinc-containing insulin storage granules of pancreatic beta-cells, solubilization of insulin would be induced. Such an event would lead to osmotic stress and eventually to rupture of the granule. The effects of diethyldithiocarbamate (DDC), an agent that has been found to protect rabbits against the induction of diabetes by some other zinc-chelating agents, were also studied. DDC caused a decrease of 3.5 units in the intravesicular pH of zinc-containing vesicles by a mechanism not involving the release of protons upon chelation of zinc. We have demonstrated several properties of DDC which may contribute to its ability to protect against the induction of diabetes. These include its ability to store zinc as a hydrophobic complex in membranes, its consumption of protons upon spontaneous decomposition, and the ability of one of its decomposition products, diethylamine, to accelerate the dissipation of pH gradients across lipid bilayers. Diethylamine is particularly effective in stimulating a rapid dissipation of such pH gradients, even at micromolar concentrations. We have attempted to estimate quantitatively the extent of proton liberation by various zinc-chelating agents. This analysis demonstrated that partitioning of the ligand between organic and aqueous phases, ligand acidity, and zinc complex stability determine the extent of proton release.
Mol Pharmacol 1985 Mar
PMID:Mechanism of action of diabetogenic zinc-chelating agents. Model system studies. 388 28

Phosphocalmodulin (PCaM) was identified after analysis of calmodulin (CaM) preparations by two-dimensional gel electrophoresis by using a modified ampholyte system to resolve very acidic proteins. The analysis of CaM prepared by the conventional procedure based upon its heat resistance and acidity as well as the analysis of whole urea extracts from brain showed that PCaM was a major component in this tissue. PCaM was 1 pH unit more acidic than CaM, and its electrophoretic mobility, unlike CaM, was not changed by either calcium or ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid. In urea extracts of brain prepared in buffers containing phosphate and sodium fluoride, PCaM was as prominent as CaM; it was partially converted into CaM after elution from the gel and reelectrophoresis. Amino acid analysis of PCaM and CaM purified by two-dimensional gel electrophoresis showed the same composition for the two proteins, including their trimethyllysine content. Incorporation of 32P occurred exclusively into the acidic variant when brain slices were incubated with H332PO4; amino acid analysis showed that the phosphate was bound to serine residues. CaM was found also to be phosphorylated in vitro by a phosphorylase kinase preparation from skeletal muscle.
Mol Cell Biol 1983 Aug
PMID:Evidence for a phosphorylated form of calmodulin in chicken brain and muscle. 662 32

Salicylhydroxamic acid (SHAM) and glycerol, when administered together, cause destruction of bloodstream forms of Trypanosoma brucei brucei, both in vitro and in vivo, but the dose required is exceedingly high. In an attempt to improve the efficacy of this drug combination, we examined the ability of various polyols and hydroxamic acids to substitute for glycerol and SHAM, respectively. No satisfactory substitute for glycerol was found. The inhibition of the trypanosomal alpha-glycerophosphate oxidase system (GPO) by SHAM (Ki 21 microM) was uncompetitive. Only primary and secondary aromatic hydroxamates were inhibitory. Among a series of 19 benzhydroxamates, no correlation existed between their acidity or their affinity for iron and their inhibition of the GPO in a cell free preparation. The Ki's of most of the primary hydroxamates ranged from 10 to 24 microM, with the more lipophilic derivatives being slightly more active. The Ki's of secondary hydroxamates were more variable, the best having Ki's of about 10 microM. Several other classes of iron chelators were also evaluated. Tropolones were active with 3-bromo-4,5-benzotropolone being as active as SHAM. 3,4-Dihydroxybenzaldehyde (Ki 15 microM) also inhibited the GPO. On the other hand, diphenylamine and 8-hydroxyquinoline, known inhibitors of the GPO, were 30 to 50 times less active. The results suggest that a lipophilic aromatic iron-chelating agent may be useful as a substitute for SHAM in combination therapy.
Mol Biochem Parasitol 1981 Sep
PMID:Trypanosoma brucei brucei: a systematic screening for alternatives to the salicylhydroxamic acid-glycerol combination. 679 1

The DNA thermal denaturation in acidic medium has been investigated experimentally and theoretically. The formulae describing a dependence of the helix--coil transition parameters (melting temperature (Tm) and melting range width (delta T) on ionisation constants values of all kinds of DNA bases in the helix and coil regions and medium acidity have been obtained. Dependences Tm (pH) and delta T (pH) have been determined experimentally and calculated for different models of protonation. Based on the comparison of theoretical and experimental dependences Tm (pH) and delta T (pH) a strict examination of the theory is conducted. The mechanism of DNA protonation is discussed.
Mol Biol (Mosk)
PMID:[Effect of selectively reacting ligands on the helix-coil transition of DNA. IV. Heat denaturation of DNA in an acid medium]. 730 Aug 28

Semi-dominant mutations in the amdA gene lead to elevated expression of the gene encoding acetamidase, amdS. These mutations also cause constitutive expression of the acetate-inducible gene, aciA. In the amdS 5' regulatory region, two cis-acting mutations, amdl66 and amdl666, have been isolated which specifically affect amdA activation of amdS. These mutations are a duplication and a triplication of an 18 bp GA-rich sequence, thought to define the amdA site of action within the amdS promoter region. Similar GA-rich sequences have also been found in the 5' region of aciA. This paper describes the cloning and initial functional characterization of the amdA gene and two of its mutant alleles. The wild-type amdA gene has been cloned by a chromosome walk from genes gatA and alcC on linkage group VII and localized by complementation of an amdA loss-of-function mutation. Transcriptional analysis reveals that the gene is expressed constitutively at low levels under growth conditions which affect expression of amdS and aciA. The gene is predicted to encode an 880-amino-acid protein which contains two C2H2 zinc fingers, a nuclear localization sequence and two transcriptional activation domains. The amdA7 semi-dominant gain-of-function mutation results in a glycine to aspartate substitution which would increase the acidity of one of these regions. Analysis of in vitro generated mutations in the 5' region of amdS using an amdS::lacZ reporter has been used to localize the site of action of AmdA. The C2H2 zinc-finger motifs identified in the protein are similar to those found in the carbon catabolite repressor protein, CreA, which also regulates amdS and recognizes sequences which overlap with the proposed site of action for AmdA.
Mol Microbiol 1995 Mar
PMID:The positively acting amdA gene of Aspergillus nidulans encodes a protein with two C2H2 zinc-finger motifs. 759 97


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