Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The high-resolution infrared spectrum of perchloric acid has been observed in the 700-750 cm-1 region using the infrared beamline at the MAX-I electron storage ring in Lund, Sweden. The spectrum displays extensive rotational structure due to a type a band and is assigned to nu5, the HO-ClO3 stretch. Approximately 1100 transitions in H35ClO4 and ca. 300 in H37ClO4 have been fitted using single subband analysis, generating constants for transitions having the same K. The origin of H35ClO4 K = 3t series is found to be 726.9971(4) cm-1. Rotationally resolved infrared line positions are now available for the identification of HClO4 in the atmosphere, which may be produced by the heterogeneous oxidation of chlorine containing species in the stratosphere. Copyright 1998 Academic Press.
J Mol Spectrosc 1998 Aug
PMID:The nu5 Band of HClO4 966 19

The visible electronic transitions of AuCl were observed at high resolution for the first time. The spectrum was recorded with the Fourier transform spectrometer associated with the McMath-Pierce solar telescope at Kitt Peak. The excited AuCl molecules were produced in a microwave discharge, with 4 Torr of helium seeded with 3% chlorine flowing over AuCl3 powder. Constants for the X1Sigma+, AOmega = 1, and BOmega = 0(+) states of Au35Cl are presented. The AOmega = 1 and the BOmega = 0(+) states may be two spin-orbit components of a 3Pi electronic state, and molecular parameters for this excited 3Pi state also are given. Copyright 1999 Academic Press.
J Mol Spectrosc 1999 Mar
PMID:Fourier Transform Emission Spectroscopy of the Visible Transitions of AuCl. 998 81

Chloride (Cl) ion channels play a critical role in the response of both vascular smooth muscle (VSM) and endothelial (ENDO) cells to agonist stimulation. In VSM, agonist-induced Cl currents produce membrane depolarization, resulting in calcium influx through voltage-sensitive channels. ENDO cells also activate Cl currents after either agonist application or perturbation of cell volume. Although some of these currents have been characterized biophysically, the genes involved have not been identified. The CLCN family of voltage-dependent Cl channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. We used Northern-blot analysis to study the expression of these Cl channel genes in cultured human aortic and coronary VSM cells and in aortic ENDO cells. CLCN3 is by far the most abundant CLC channel mRNA in both VSM and ENDO cells. Lower levels of expression are seen for CLCN2, CLCN4, CLCN5 and CLCN6. Expression levels were similar in VSM and ENDO cells except for CLCN4 which was more highly expressed in ENDO cells. In situ hybridization was used to confirm the expression of CLCN3 in intact human fetal lung. CLCN3 message was seen in VSM and ENDO cells of both large and small pulmonary vessels, indicating that their detection by Northern blotting was not an artifact of cell culture. CLCN3 is also expressed in pulmonary epithelial and bronchial smooth muscle cells but not in chondrocytes or pulmonary interstitial cells. Recent studies suggest that CLCN3 may encode the swelling-induced Cl conductance. We used whole cell patch clamp recording to demonstrate swelling-induced Cl currents in these cultured VSM cells. This suggests that the CLCN3 protein is expressed; however, the functional role of this current in VSM remains to be determined.
J Mol Cell Cardiol 1999 Mar
PMID:Expression of CLCN voltage-gated chloride channel genes in human blood vessels. 1019 95

PGHS-1 and PGHS-2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs). It appears that the high degree of selectivity for inhibition of PGHS-2 shown by certain compounds is the result of two mechanisms (time-dependent and time-independent inhibition), by which they interact with each isoform. The fenamic acids can be divided into competitive inhibitors of substrate binding and competitive inhibitors that cause time-dependent losses of cyclooxygenase activity. The cyclooxygenase activity was measured by oxygen consumption following preincubation of the enzyme and the inhibitor for increasing periods of time. The rate constants associated with binding inhibition kinetics and structure-activity relationships were calculated for a large number of fenamates, diclofenac and indomethacin. The K1* values are similar but the individual rate constants are markedly different: K1 is two-fold lower, and k2 is six-fold slower for diclofenac than for indomethacin. All the active time-dependent compounds show MEPs with a negative conical surface, with their vertex on the minimum of the carboxyl group, which extends around the first aromatic ring to the central region. The conical surface keeps an open angle of 61 degrees or larger, and a close contact surface with the residues Ala527, Ileu523, Val349, and Ser530, in the zones surrounding the bridging amino group and the chlorine atoms for meclofenamate and diclofenac, or in the region around the carbonyl group for indomethacin. The K1* and IC50 values indicate that the interactions that promote the slow binding kinetics must be examined in relation to the reaction energies of formation (delta Hr) of an ionic bond between the deprotonated carboxylic acid group of acid NSAIDs with the monocationic guanidinum group of Arg120, the free energies of solvation in aqueous solution, and the molecular volumes measured. Presumably indomethacin, diclofenac and meclofenamate cause the enzyme to undergo a subtle conformational change to a form that binds compounds even more tightly, with some slight structural changes confined to reorientations of the Arg277 and Gln358 side chains. These results show that the model has reliably chosen regions of biological significance consistent with both the X-ray crystallographic and kinetic results.
J Comput Aided Mol Des 1999 May
PMID:The structural and electronical factors that contribute affinity for the time-dependent inhibition of PGHS-1 by indomethacin, diclofenac and fenamates. 1021 35

A general method for solving the phase problem from native crystals of macromolecules has long eluded structural biology. For well diffracting crystals this goal can now be achieved, as is shown here, thanks to modern data collection techniques and new statistical phasing algorithms. Using solely a native crystal of tetragonal hen egg-white lysozyme, a protein of 14 kDa molecular mass, it was possible to detect the positions of the ten sulfur and seven chlorine atoms from their anomalous signal, and proceed from there to obtain an electron-density map of very high quality.
J Mol Biol 1999 May 28
PMID:Can anomalous signal of sulfur become a tool for solving protein crystal structures? 1033 7

The control of steroidogenesis via signal transduction mechanisms involving cAMP-dependent and cAMP-independent mechanisms is reviewed. Several structurally unrelated factors that are potent stimulators of steroidogenesis whose actions do not require cAMP and/or synthesis of proteins have been identified. These include various interleukins, a lipophilic factor from macrophages, a steroidogenic inducing protein from follicular fluid and an imidazole compound, calmidazolium. All of these factors are capable of inducing maximum steroidogenesis. Calcium is required for steroidogenesis in all steroidogenic cells. With the exception of the effects of angiotensin II, there is little evidence for a role of IP3 in the stimulation of the release of calcium from intracellular stores in steroidogenic cells under physiological conditions. There may however, be a cAMP-mediated activation of a plasma membrane calcium channel. Chloride channels that can be regulated by cAMP-dependent and -independent mechanisms, are present in steroidogenic cells. Chloride ions exert a negative effect on steroidogenesis because exclusion of chloride from the extracellular medium markedly enhances cAMP-stimulated steroidogenesis. Arachidonic acid and its lipoxygenase products are involved in the control of steroidogenesis via cAMP mediated processes. An arachidonic acid related thioesterase has been isolated that is activated by ACTH and which may be involved in the release of arachidonic acid. It is concluded that while cAMP is a second messenger for LH/ACTH in the control of steroidogenesis, other signalling systems exist which are potentially equally effective in controlling steroidogenesis. In addition, the action of cAMP requires other signalling pathways involving calcium and chloride ions, as well as arachidonic acid and its lipoxygenase products.
Mol Cell Endocrinol 1999 May 25
PMID:Signal transduction involving cyclic AMP-dependent and cyclic AMP-independent mechanisms in the control of steroidogenesis. 1041 17

A species-specific Peptide Nucleic Acid (PNA) oligonucleotide probe directed against the V(1)region of the 16S rRNA molecule was synthesized for the detection of Escherichia coli in water. The specificity of the probe was tested in dot blot hybridizations against a number of environmental isolates including those from the genera Escherichia, Klebsiella, Enterobacter and Citrobacter. In situ hybridization experiments were performed with biotinylated PNA oligonucleotide probes with subsequent detection of the biotin label using a combination of Streptavidin-Horseradish Peroxidase and a tyramide signal amplification system. The results obtained enabled the specific detection of E. coli in under 3 h. Hybridizations were also performed on cells which were treated with chlorine (1.5 mg l(-1)) for up to 30 min. Escherichia coli cells were still detected after storage for 14 days at room temperature. No cells were detected by conventional plate count or the <<Colilert>> assay, a method currently used for the routine detection of E. coli and coliforms in the water industry. Cell viability was assessed by the ability of cells to reduce 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) to highly fluorescent formazan crystals through bacterial respiration. Only cells that had not been chlorinated were detected. These results confirm that ribosomal RNA exists within the cell long after cell death has occurred and that rRNA cannot be used to assess the viability of individual cells. However rRNA probes in combination with viability markers should enable the specific detection of viable cells in situ. Hybridization experiments were also performed successfully on seeded tap water samples. The number of fluorescent cells detected correlated well with those obtained by plate count analysis. This represents the first reported use of PNA oligonucleotides for in situ detection of micro-organisms and offers a fast efficient alternative to conventional DNA approaches.
Mol Cell Probes 1999 Aug
PMID:Use of PNA oligonucleotides for the in situ detection of Escherichia coli in water. 1044 Nov 98

The Ussing chamber technique was used for studying unidirectional fluxes of 14C-butyrate across the bovine rumen epithelium in vitro. Significant amounts of butyrate were absorbed across the bovine rumen epithelium in vitro, without any external driving force. The paracellular pathway was quantitatively insignificant. The transcellular pathway was predominately voltage-insensitive. The serosal to mucosal (SM) pathway was regulated by mass action, whereas the mucosal to serosal (MS) pathway further includes a saturable process, which accounted for 30 to 55% of the MS flux. The studied transport process for 14C-butyrate across the epithelium could include metabolic processes and transport of 14C-labelled butyrate metabolites. The transport of butyrate interacted with Na+, Cl- and HCO3-, and there was a linear relationship between butyrate and sodium net transport. Lowering the sodium concentration from 140 to 10 mmol l-1 decreased the butyrate MS flux significantly. Amiloride (1 mmol l-1) did, however, not reduce the butyrate flux significantly. Chloride concentration in itself did not seem to influence the transport of butyrate, but chloride-free conditions tended to increase the MS and SM flux of butyrate by a DIDS-sensitive pathway. DIDS (bilateral 0.5 mmol l-1) did further decrease the butyrate SM flux significantly at all chloride concentrations. Removing bicarbonate from the experimental solutions decreased the MS and increased the SM flux of butyrate significantly, and abolished net butyrate flux. There were no significant effects of the carbonic anhydrase inhibitor Acetazolamide (bilateral 1.0 mmol l-1). The results can be explained by a model where butyrate and butyrate metabolites are transported both by passive diffusion and by an electroneutral anion-exchange with bicarbonate. The model couples sodium and butyrate via CO2 from metabolism of butyrate, and intracellular pH.
Comp Biochem Physiol A Mol Integr Physiol 1999 Aug
PMID:Transport of butyrate across the isolated bovine rumen epithelium--interaction with sodium, chloride and bicarbonate. 1058 5

Anomalous diffraction with soft X-ray synchrotron radiation opens new possibilities in protein crystallography and materials science. Low-Z elements like silicon, phosphorus, sulfur and chlorine become accessible as new labels in structural studies. Some of the heavy elements like uranium exhibit an unusually strong dispersion at their M(V) absorption edge (lambdaMV = 3.497 A, E(MV) = 3545 eV) and so does thorium. Two different test experiments are reported here showing the feasibility of anomalous X-ray diffraction at long wavelengths with a protein containing uranium and with a salt containing chlorine atoms. With 110 electrons the anomalous scattering amplitude of uranium exceeds by a factor of 4 the resonance scattering of other strong anomalous scatterers like that of the lanthanides at their L(III) edge. The resulting exceptional phasing power of uranium is most attractive in protein crystallography using the multi-wavelength anomalous diffraction (MAD) method. The anomalous dispersion of an uranium derivative of asparaginyl-tRNA synthetase (hexagonal unit cell; a = 123.4 A, c = 124.4 A) has been measured for the first time at 4 wavelengths near the M(V) edge using the beamline ID1 of ESRF (Grenoble, France). The present set up allowed to measure only 30% of the possible reflections at a resolution of 4 A, mainly because of the low sensitivity of the CCD detector. In the second experiment, the dispersion of the intensity of 5 X-ray diffraction peaks from pentakismethylammonium undecachlorodibismuthate (PMACB, orthorhombic unit cell; a = 13.003 A, b = 14.038 A, c = 15.450 A) has been measured at 30 wavelengths near the K absorption edge of chlorine (lambdaK = 4.397 A, EK= 2819.6 eV). All reflections within the resolution range from 6.4 A to 3.4 A expected in the 20 degree scan were observed. The chemical state varies between different chlorine atoms of PMACB, and so does the dispersion of different Bragg peaks near the K-edge of chlorine. The results reflect the performance of the beamline ID1 of ESRF at wavelengths beyond 3 A at the end of 1998. A gain by a factor 100 for diffraction experiments with 4.4 A photons was achieved in Autumn 1999 when two focusing mirrors had been added to the X-ray optics. Further progress is expected from area detectors more sensitive to soft X-rays. Both CCD detectors and image plates would provide a gain of two orders of measured intensity. Image plates would have the additional advantage that they can be bent cylindrically and thus cover a larger solid angle in reciprocal space. In many cases, samples need to be cooled: closed and open systems are presented. A comparison with the state of art of soft X-ray diffraction, as it had been reached at HASYLAB (Hamburg, Germany), and as it is developing at the Brookhaven National Laboratory (USA), is given.
Cell Mol Biol (Noisy-le-grand) 2000 Jul
PMID:Anomalous X-ray diffraction with soft X-ray synchrotron radiation. 1097 74

A new crystal structure of O-acetylserine sulfhydrylase (OASS) has been solved with chloride bound at an allosteric site and sulfate bound at the active site. The bound anions result in a new "inhibited" conformation, that differs from the "open" native or "closed" external aldimine conformations. The allosteric site is located at the OASS dimer interface. The new inhibited structure involves a change in the position of the "moveable domain" (residues 87-131) to a location that differs from that in the open or closed forms. Formation of the external aldimine with substrate is stabilized by interaction of the alpha-carboxyl group of the substrate with a substrate-binding loop that is part of the moveable domain. The inhibited conformation prevents the substrate-binding loop from interacting with the alpha-carboxyl group, and hinders formation of the external Schiff base and thus subsequent chemistry. Chloride may be an analog of sulfide, the physiological inhibitor. Finally, these results suggest that OASS represents a new class of PLP-dependent enzymes that is regulated by small anions.
J Mol Biol 2000 Oct 20
PMID:Identification of an allosteric anion-binding site on O-acetylserine sulfhydrylase: structure of the enzyme with chloride bound. 1102 92


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