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)

X-ray fiber diffraction patterns of the R-type straight flagellar filament of Salmonella typhimurium SJW1655 strain showed layer-lines with an axial spacing of 1/437 A-1, which could be resolved only due to very small disorientation angles (< 2 degrees) of the filaments in oriented sol specimens. Although the equatorial layer-line was situated between the relatively strong first layer-lines right above and below it, these small disorientation angles and a new method of two-dimensional angular deconvolution allowed us to determine the equatorial layer-line intensities quite accurately. The equatorial data were phased by using the amplitude difference between the native flagellar filament and its heavy atom derivatives. One of the heavy-atom derivatives was prepared by introducing a cysteine residue by site-directed mutagenesis and applying a mercury compound. From the equatorial structure factors, the radial density distribution of the filament was calculated at 11 A resolution. A prominent feature was two pairs of high density peaks at radii of around 25 and 45 A and a deep density trough between them, which corresponds to the concentric double tubular structure in the core region that has been found in the density map recently deduced by helical image reconstruction from electron micrographs of frozen hydrated filaments. The molecular masses were estimated for four radial segments that correspond to the morphological domains identified in the map of helical image reconstruction. Then the domains were assigned to sequence positions by correlating the estimated masses with those of proteolytic fragments of flagellin. The assignment is consistent with the distributions of secondary structures and in particular alpha-helical coiled-coils that were predicted from the sequence. It also helps to understand how the polymerization behaviour is affected by truncation of the disordered terminal regions of flagellin and why mutations in a specific region are responsible for changes in the polymorphic shape of the filament.
J Mol Biol 1995 Nov 03
PMID:Radial mass analysis of the flagellar filament of Salmonella: implications for the subunit folding. 747 33

Each cysteine residue in the MerT and MerP polypeptides of bacterial transposon Tn501 was replaced by serine, and the mercury-resistance phenotypes of the mutants were determined in Escherichia coli. Cys-24 and Cys-25 in the first transmembrane region of MerT were essential for transport of mercuric ions through the cytoplasmic membrane, and mutations Cys-76-Ser, Cys-82-Ser or Gly-38-Asp in MerT or Cys-36-Ser in MerP all reduced transport and resistance. Deletion of the merP gene slightly reduced mercuric ion resistance and transport, whereas a Cys-33-Ser mutation in MerP appears to block transport of mercuric ions by MerT. The effects of deleting merP on mutations in merT were tested. The 116-amino-acid MerT protein is sufficient for mercuric ion transport across the cytoplasmic membrane.
Mol Microbiol 1995 Jul
PMID:The role of cysteine residues in the transport of mercuric ions by the Tn501 MerT and MerP mercury-resistance proteins. 747 6

1. Growth cones of cultured dorsal root ganglion neurons from mice were irradiated using a mercury lamp. 2. The flux of particles of fast retrograde axoplasmic transport decreased promptly after light irradiation without a change in velocity. 3. That of anterograde transport decreased as well, but with a significant latency. The decrease in anterograde flux was attributed to decreased velocity of particles. 4. Video-enhanced contrast microscopy of growth cones revealed transient swelling of growth cones and transient stagnation of particles in growth cones. 5. The longer the neurite, the larger the latency of the change of the anterograde transport; peripheral information was calculated to be conveyed to the cell body at a speed of 6 microns/min. 6. The mechanism of this information conveyance and the export of materials from the cell body are discussed.
Cell Mol Neurobiol 1995 Jun
PMID:Differential suppression of axoplasmic transport: effects of light irradiation to the growth cone of cultured dorsal root ganglion neurons. 755 30

In Alcaligenes eutrophus JMP134, pJP4 carries the genes coding for 2,4-dichlorophenoxyacetate (2,4-D) and 3-chlorobenzoate (3-Cba) degradation plus mercury resistance. The plasmid genes specifying 2,4-D and 3-Cba catabolism are organized in three operons: tfdA, tfdB, and tfdCDEF. Regulation of these operons by two unlinked genes, tfdR and tfdS, has been proposed. Physical and DNA sequence analyses revealed that the tfdR and tfdS genes were identical and were located within a longer inverted repeat of 1592 bp. Similar stem-loop structures were observed among other 2,4-D plasmids. The tfdR gene is 888 bp long and capable of encoding a polypeptide of 32 kDa. The deduced amino acid sequence of tfdR indicates that it is a member of the LysR-type activators. Investigation of the regulation of the catabolic gene clusters through the construction of a pJP4 defined deletion mutant, pYG1010, which lacks a 4.2 kilobase Xbal fragment containing the inverted repeat region carrying the tfdR and tfdS regulatory genes, showed that Pseudomonas cepacia strains containing pYG1010 became 2,4-D negative, but 3-Cba positive. In vivo recombinants of pYG1010 and a cloned tfdS gene rescued the 2,4-D phenotype, indicating that TfdS is a positive regulator of tfdA expression, but not for tfdCDEF expression.
Mol Microbiol 1995 Apr
PMID:Genetic and molecular analysis of a regulatory region of the herbicide 2,4-dichlorophenoxyacetate catabolic plasmid pJP4. 756 94

Individual merRT delta P regions were amplified from DNA directly isolated from soil and sediment samples using consensus primers derived from the conserved mer sequences of Tn501, Tn21 and pMER419. Soil and sediment samples were taken from four sites in the British Isles; one 'pristine' (SB) and three polluted (SO, SE, T2) with respect to mercury. The sizes of the PCR products amplified (approximately 1 kb) were consistent with their generation from mer determinants related to the archetypal elements found in Gram negative bacteria. Forty-five individual clones of sequences obtained from these four sites were isolated which hybridized (> 70% homology) to a merRT delta P probe from Tn501. The diversity of these amplified mer genes was analysed using Restriction Fragment Length Polymorphism (RFLP) profiling. Fourteen RFLP classes were distinguished, 12 of which proved to be novel and only two of which had been identified in an earlier study of 40 Gram negative mercury resistant bacteria cultured from the same four sites. UPGMA analysis was used to examine the relationships between the 22 classes of determinant identified. The T2 site, which has the longest history of mercury exposure, was found to have the greatest level of diversity in terms of numbers of classes of determinant, while the SO site, which had the highest mercury levels showed relatively low variation. Variation of mer genes within and between the sequences from cultivated bacteria and from total bacterial DNA shows clearly that analysing only sequences from cultivated organisms results in a gross underestimation of genetic variation.
Mol Ecol 1995 Oct
PMID:Genetic diversity within mer genes directly amplified from communities of noncultivated soil and sediment bacteria. 758 68

1. The GABAA receptor-chloride channel complex has been shown to be modulated by a variety of chemicals. Scores of chemicals with diverse and unrelated structures augment the GABA-induced chloride current, while some other chemicals suppress the current. Certain heavy metals and a variety of polyvalent cations increase or decrease the current in a potent and efficacious manner. 2. We have studied the mechanisms whereby mercury, copper, zinc, and lanthanides modulated the GABA system by whole-cell and single-channel patch clamp techniques as applied to the rat dorsal root ganglion neurons in primary culture. 3. Mercuric chloride augmented the GABA-induced current to 115% of control at 0.1 microM and to 270% of control at 100 microM. It also generated a slowly developing inward current carried by a variety of ions. In contrast, methylmercury suppressed the GABA-induced current. The potent stimulation of the GABA system by mercuric chloride is deemed important in mercury intoxication. 4. Copper and zinc suppressed the GABA-induced current with an EC50 of 16 and 19 microM, respectively. They bound to a common site on the external surface of the GABA receptor-channel complex. 5. Lanthanum augmented the GABA-induced current with an EC50 of 230 microM by increasing the affinity of the receptor for GABA. It bound to a site on or near the external surface of the GABA receptor-channel complex which is different from the sites for GABA, barbiturates, benzodiazepines, picrotoxin, and copper/zinc. 6. Six other lanthanides with larger atomic numbers also exerted the same stimulatory effect with their efficacies increasing with the atomic number. 7. Single-channel analyses have revealed that the augmentation of whole-cell current by terbium, a lanthanide, is due to three actions: an increase in the overall mean open time, a decrease in the overall mean closed time, and an increase in the overall mean burst time.
Cell Mol Neurobiol 1994 Dec
PMID:GABA receptor-channel complex as a target site of mercury, copper, zinc, and lanthanides. 764 Dec 24

1. Using conventional two-microelectrode voltage-clamp techniques we studied the effects of inorganic mercury (HgCl2) on acetylcholine-, carbachol-, and glutamate-activated currents on Aplysia neurons. Hg2+ was applied with microperfusion. 2. Acetylcholine and carbachol activated an inward, sodium-dependent current in the anterior neurons of the pleural ganglion. The medial neurons gave a biphasic current to acetylcholine and carbachol, which was outward at resting membrane potential. The faster component was Cl- dependent and reversed at about -60 mV, while the slower component was K+ dependent and reversed at greater than -80 mV. 3. Hg2+ (0.1-10 microM) caused a dramatic increase in the acetylcholine- and carbachol-induced inward current in anterior neurons and the fast Cl- current in medial neurons. With only a 1-min preapplication of Hg2+, the acetylcholine- or carbachol-activated sodium or chloride currents were increased to 300% and the effect was only partly reversible. The threshold concentration was 0.1 microM Hg2+. 4. Contrary to the effects on sodium and chloride currents, concentrations of 0.1-10 microM Hg2+ caused a complete and irreversible blockade of K(+)-dependent acetylcholine and carbachol currents. The block of the potassium current was relatively fast and increased with time. The concentration of HgCl2 that gave a half-maximal blockade of the carbachol-activated potassium current was 0.89 microM. The chloride-dependent current elicited by glutamate on medial neurons was increased by HgCl2 as well. 5. These results suggest that actions at agonist-activated channels must be considered as contributing to mercury neurotoxicity. It is possible that the toxic actions of Hg2+ on synaptic transmission at both pre- and postsynaptic sites are important factors in the mechanism of Hg2+ toxicity.
Cell Mol Neurobiol 1994 Dec
PMID:Effect of HgCl2 on acetylcholine, carbachol, and glutamate currents of Aplysia neurons. 764 Dec 26

1. We examined the actions of mercury (Hg2+) and zinc (Zn2+) on voltage-activated calcium channel currents of cultured rat dorsal root ganglion (DRG) neurons, using the whole-cell patch clamp technique. 2. Micromolar concentrations of both cations reduced voltage-activated calcium channel currents. Calcium channel currents elicited by voltage jumps from a holding potential of -80 to 0 mV (mainly L- and N-currents) were reduced by Hg2+ and Zn2+. The threshold concentration for Hg2+ effects was 0.1 microM and that for Zn2+ was 10 microM. Voltage-activated calcium channel currents were abolished (> 80%) with 5 microM Hg2+ or 200 microM Zn2+. The peak calcium current was reduced to 50% (IC50) by 1.1 microM Hg2+ or 69 microM Zn2+. While Zn2+ was much more effective in reducing the T-type calcium channel current--activated by jumping from -80 to -35 mV--Hg2+ showed some increased effectiveness in reducing this current. 3. The effects of both cations occurred rapidly and a steady state was reached within 1-3 min. While the action of Zn2+ was not dependent on an open channel state, Hg2+ effects depended partially on channel activation. 4. While both metal cations reduced the calcium channel currents over the whole voltage range, some charge screening effects were detected with Hg2+ and with higher concentrations (> 100 microM) of Zn2+. 5. As Zn2+ in the concentration range used had no influence on resting membrane currents, Hg2+ caused a clear inward current at concentrations > or 2 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
Cell Mol Neurobiol 1994 Dec
PMID:Mercury (Hg2+) and zinc (Zn2+): two divalent cations with different actions on voltage-activated calcium channel currents. 764 Dec 28

1. The effects of heavy metals (Pb2+, Hg2+, and Zn2+) on synaptic transmission in the identified neural network of Helix pomatia L. and Lymnaea stagnalis L. (Gastropoda, Mollusca) were studied, with investigation of effects on inputs and outputs as well as on interneuronal connections. 2. The sensory input running from the cardiorenal system to the central nervous system and the synaptic connections between central neurons were affected by heavy metals. 3. Lead and mercury (10(-5)-10(-3) M) eliminated first the inhibitory, then the excitatory inputs running from the heart to central neurons. At the onset of action lead increased the amplitude of the excitatory postsynaptic potentials, but blockade of sensory information transfer occurred after 10-20 min of treatment. 4. The monosynaptic connections between identified interneurons were inhibited by lead and mercury but not by zinc. Motoneurons were found to be less sensitive to heavy metal treatment than interneurons or sensory pathways. 5. The treatment with Pb2+ and Hg2+ often elicited pacemaker and bursting-type firing in central neurons, accompanied by disconnection of synaptic pathways, manifested by insensitivity to sensory synaptic influences. 6. Zn2+ treatment also sometimes induced pacemaker activity and burst firing but did not cause disconnection of the synaptic transmission between interneurons. 7. A network analysis of heavy metal effects can be a useful tool in understanding the connection between their cellular and their behavioral modulatory influences.
Cell Mol Neurobiol 1994 Dec
PMID:Modulation of synaptic events by heavy metals in the central nervous system of mollusks. 764 Dec 33

Proliferating cell nuclear antigen (PCNA) is the component of the chromosomal DNA replication machinery in eukaryotic cells that confers high processivity upon DNA polymerase delta and epsilon. It has been proposed that PCNA functions by forming a trimeric complex with a ring-like structure through which DNA is threaded. PCNA from the yeast Saccharomyces cerevisiae has been crystallized in a cubic space group (P2(1)3, a = 121.1 A). Unexpectedly, a mercury derivative of PCNA yields crystals that diffract significantly better than crystals of the unmodified protein (2.4 A and 3.0 A resolution, respectively). Mass spectrometry reveals that the derivative results from the addition of two mercury atoms to the protein. Although crystals of the mercurated protein show evidence of non-isomorphism, the anomalous diffraction signal is strong and phases may be determined by multi-wavelength anomalous diffraction (MAD phasing).
J Mol Biol 1994 Aug 12
PMID:Crystallization of proliferating cell nuclear antigen (PCNA) from Saccharomyces cerevisiae. 791 45


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