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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of the refractive properties of Gramicidin A in absolute ethanol and in ethanol water mixtures showed that this peptide in solution undergoes a conformational transition resulting in species with different refractivity. Accordingly, the folded form of this peptide shows a lower specific refractive index increment than the unfolded form. In addition, the occurrence of a strong pressure dependence of the transition is documented.
Mol Biol Rep 1975 Jul
PMID:Anomalous refractivity changes of gramicidin A in ethanol solutions. 5 70

The sodium channel activators veratridine and batrachotoxin, the sodium ionophore gramicidin, and the calcium ionophore ionomycin stimulated phosphoinositide breakdown, as indicated by the increased accumulation of [3H]inositol monophosphate in embryonic chick heart cells. The levels of [3H]inositol trisphosphate and [3H]inositol bisphosphate were also increased by veratridine, indicating that there was increased hydrolysis of phosphatidylinositol bisphosphate by phospholipase C. The response to veratridine required both extracellular sodium and calcium, suggesting that calcium entry via Na/Ca exchange might activate phospholipase C. Fluorescence measurements with fura-2 confirmed that the sodium agents greatly increased the cytoplasmic calcium concentration. Veratridine (100 microM) increased cytoplasmic calcium from 94 +/- 4 nM to 862 +/- 103 nM, giving a maximal calcium increase in about 2 min. Batrachotoxin (1 microM) induced an even greater increase in calcium but required a longer time. Gramicidin also induced a large increase in cytoplasmic calcium which was maximal within 0.5 min. To directly test the calcium dependency of phospholipase C, we permeabilized the chick heart cells with saponin and monitored the production of inositol phosphates at different calcium concentrations. Raising the calcium concentration from 3 to 1000 nM increased the accumulation of [3H]inositol phosphates by nearly 4-fold with a half-maximal effect at about 200 nM calcium. The guanine nucleotide guanosine-5'-O-(3-thio)triphosphate (GTP gamma S) also stimulated accumulation of the InsPs and the response to (GTP gamma S) was potentiated by increasing the calcium concentration. The data suggest that the effect of the sodium agents on phosphoinositide hydrolysis results from an elevation of intracellular calcium which increases GTP-dependent phospholipase C activity. Thus, drugs or other conditions that elevate cytoplasmic calcium in heart cells may increase the hydrolysis of membrane phosphoinositides.
Mol Pharmacol 1988 Mar
PMID:Elevation of cytoplasmic calcium concentration stimulates hydrolysis of phosphatidylinositol bisphosphate in chick heart cells: effect of sodium channel activators. 245 Nov 16

X-ray crystal structure determinations and energy-minimization techniques provide conformational data on the complexed and uncomplexed forms of ion transport antibiotics of the shuttle and channel types. In the solid state, hexadecaisoleucinomycin (HEXIL), an analogue of valinomycin, is observed as an asymmetric macrocycle stabilized by eight intramolecular (4----1) hydrogen bonds. The structure obtained from energy-minimization procedures exhibits a greater variation in phi and psi angles of chemically equivalent residues than does the crystallographically observed structure. The structure has eight carbonyl groups directed toward its interior and is capable of providing flexible coordination to a positively charged ion or molecule. These structural findings are consistent with the observed capacity of HEXIL to complex cesium ions, tetramethyl ammonium ions and acetylcholine. Gramicidin A is a pentadecapeptide that functions as a transmembrane channel for transporting monovalent cations. Uncomplexed gramicidin A crystallizes as a left-handed, antiparallel, double-stranded, helical dimer with 5.6 amino acid residues per turn. The helix has an overall length of 31 A and an average inner channel diameter of 4.8 A. The channel of this crystalline form does not contain ions or solvent molecules. Transporting ions through this channel could be achieved only by some expansion of the channel opening that would involve breaking and reforming hydrogen bonds that stabilize the double-stranded helix.
J Mol Graph 1989 Jun
PMID:Molecular conformation and ion transport of cyclic and linear ionophores. 248 29

Plasma membrane electron transport reactions and associated proton secretion were studied in boron-deficient carrot cells. It was found that the hormone-sensitive plasma membrane NADH oxidase was inhibited by boron deficiency and that under such conditions activity could be restored by exogenous boric acid with or without 2,4-dichlorophenoxy acetic acid. Gramicidin, a channel-forming protonophore, further stimulated NADH oxidase by carrot cells. Proton secretion, associated with plasma membrane H(+)-ATPase, was also affected by boron deficiency, but not as severely as ferricyanide-generated proton secretion, reflecting plasma membrane electron transport. The addition of 1 mM boric acid and 1 microM 2,4-dichlorophenoxy acetic acid to carrot cells fully restored the H+ secretion in presence of ferricyanide. The effect of boron deficiency in cultured carrot cells can, therefore, be directly associated with cell growth through its effect on the plasma membrane NADH oxidase and H+ secretion. Ferricyanide provides a probe which activates transmembrane electron transport that is only coupled to proton release when boron is present.
Biochem Mol Biol Int 1993 Sep
PMID:The effect of boron on plasma membrane electron transport and associated proton secretion by cultured carrot cells. 750 53

The structure of a parallel left-handed double-helical form of gramicidin was detected by circular dichroism spectroscopy and determined using 500 and 600 MHz NMR in CaCl2/methanol solution. Measurements of TOCSY, DQF-COSY and NOESY spectra were converted into 604 distance and 48 torsional angle constraints for structure calculations. Stereospecific assignments and chi 1 angles were calculated using 3J alpha beta, d alpha beta (i,i), dN beta(i,i) and dN gamma(i,i). chi 2 angles were determined using d alpha beta(i,i), dN beta(i,i), d beta delta(i,i), dN gamma(i,i) and d alpha gamma(i,i). The calculations of initial structures were performed using the distance geometry/simulated annealing method in XPLOR. The initial structures were further refined and energy minimized using simulated annealing/molecular dynamics methods. Back-calculations for every generated structure were also performed to check their consistency with the experimental data. 187 final structures with no violations above the threshold conditions (0.05 A, 5 degrees, 5 degrees, 0.5 A and 5 degrees for bonds, angles, improper, NOE and cdihe, respectively) were produced from the 200 initial structures. Twenty structures with the lowest NOE energies were used for further analysis. The average r.m.s. deviations for the 20 structures are 0.64 A for backbone and 1.1 A for all non-hydrogen atoms. Gramicidin in this form, with approximately 5.7 residues per turn, is a parallel double helical dimer. The length along the helix axis is about 30 A and the inner pore diameter varies from 1 to 2 A. It is different from all other gramicidin structures determined to date. The presence of Ca2+ stabilises a conformation that prevents the binding of monovalent cations. It is likely that this structure is related to a non-channel, antibiotic role of gramicidin.
J Mol Biol 1996 Dec 13
PMID:Solution structure of a parallel left-handed double-helical gramicidin-A determined by 2D 1H NMR. 898 Jun 84

The Staphylococcus aureus cidABC and lrgAB operons have been shown to play a key role in the regulation of murein hydrolase activity and cell death in a manner thought to be analogous to bacteriophage-encoded holins and anti-holins respectively. Because of these functions, it has been proposed that the regulation of these operons is tightly controlled and responsive to key metabolic signals. The current study revealed the presence of two overlapping regulatory pathways controlling cidABC and lrgAB expression, one dependent on acetic acid and the other dependent on proton motive force (PMF). The latter pathway was analysed using agents that affect various aspects of the PMF. Gramicidin and carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimicrobial agents that dissipate the DeltapH and membrane potential (DeltaPsi), both enhanced lrgAB expression. Restoration of the PMF by incubation of the bacteria in the presence of glucose restored lrgAB expression back to the uninduced state. In addition, valinomycin, which specifically collapses the DeltaPsi, also induced lrgAB expression. In contrast, nigericin, which dissipates the DeltapH component of the PMF, was found to have a minimal effect on DeltaPsi and lrgAB transcription. Finally, the DeltaPsi-inducible expression of lrgAB was shown to be dependent on the previously characterized LytSR two-component regulatory system that is involved in the regulation of autolysis. The results of this study support a model in which the LytSR regulatory system responds to a collapse in DeltaPsi by inducing the transcription of the lrgAB operon.
Mol Microbiol 2006 Mar
PMID:The role of proton motive force in expression of the Staphylococcus aureus cid and lrg operons. 1646 84

This work presents new developments of the moving-domain QM/MM (MoD-QM/MM) method for modeling protein electrostatic potentials. The underlying goal of the method is to map the electronic density of a specific protein configuration into a point-charge distribution. Important modifications of the general strategy of the MoD-QM/MM method involve new partitioning and fitting schemes and the incorporation of dynamic effects via a single-step free energy perturbation approach (FEP). Selection of moderately sized QM domains partitioned between C (alpha) and C (from C=O), with incorporation of delocalization of electrons over neighboring domains, results in a marked improvement of the calculated molecular electrostatic potential (MEP). More importantly, we show that the evaluation of the electrostatic potential can be carried out on a dynamic framework by evaluating the free energy difference between a non-polarized MEP and a polarized MEP. A simplified form of the potassium ion channel protein Gramicidin-A from Bacillus brevis is used as the model system for the calculation of MEP.
J Mol Model 2008 Jun
PMID:Optimization of cutting schemes for the evaluation of molecular electrostatic potentials in proteins via Moving-Domain QM/MM. 1842 44

The linear pentadecapeptide gramicidin A forms an ion channel in the lipid bilayer to selectively transport monovalent cations. Nevertheless, we have surprisingly found that gramicidin A directly inhibits mammalian Na(+)/K(+)-ATPase. Gramicidin A inhibited ATP hydrolysis by Na(+)/K(+)-ATPase from porcine cerebral cortex at the IC(50) value of 8.1 microM, while gramicidin S was approximately fivefold less active. The synthetic gramicidin A analog lacking N-terminal formylation and C-terminal ethanolamine exhibited a weaker inhibitory effect on the ATP-hydrolyzing activity of Na(+)/K(+)-ATPase than gramicidin A, indicating that these end modifications are necessary for gramicidin A to inhibit Na(+)/K(+)-ATPase activity. Moreover, Lineweaver-Burk analysis showed that gramicidin A exhibits a mixed type of inhibition. In addition to the most well-studied ionophore activity, our present study has disclosed a novel biological function of gramicidin A as a direct inhibitor of mammalian Na(+)/K(+)-ATPase activity.
Mol Cell Biochem 2008 Dec
PMID:Gramicidin A directly inhibits mammalian Na(+)/K (+)-ATPase. 1862 37

Ion channels have gained increased interest as therapeutic targets over recent years, since a growing number of human and animal diseases have been attributed to defects in ion channel function. Potassium channels are the largest and most diverse family of ion channels. Pharmaceutical agents such as Glibenclamide, an inhibitor of K(ATP) channel activity which promotes insulin release, have been successfully sold on the market for many years. So far, only a small group of the known ion channels have been addressed as potential drug targets. The functional testing of drugs on these ion channels has always been the bottleneck in the development of these types of pharmaceutical compounds.New generations of automated patch clamp screening platforms allow a higher throughput for drug testing and widen this bottleneck. Due to their planar chip design not only is a higher throughput achieved, but new applications have also become possible. One of the advantages of planar patch clamp is the possibility of perfusing the intracellular side of the membrane during a patch clamp experiment in the whole-cell configuration. Furthermore, the extracellular membrane remains accessible for compound application during the experiment.Internal perfusion can be used not only for patch clamp experiments with cell membranes, but also for those with artificial lipid bilayers. In this chapter we describe how internal perfusion can be applied to potassium channels expressed in Jurkat cells, and to Gramicidin channels reconstituted in a lipid bilayer.
Methods Mol Biol 2008
PMID:Planar patch clamp: advances in electrophysiology. 1899 92

The cation-Cl(-) cotransporters participate to neuronal Cl(-) balance and are responsible for the post-natal Cl(-) switch in central neurons. In the adult peripheral nervous system, it is not well established whether a Cl(-) transition occurs during maturation. We investigated the contribution of cation-Cl(-) cotransporters in the Cl(-) handling of sensory neurons derived from the dorsal root ganglia (DRG) of neonatal mice (postnatal days 1-6) and adult mice. Gramicidin-perforated patch-clamp recordings in wild-type neurons revealed that Cl(-) accumulated to very high values in P1-6 sensory neurons and decreased in adulthood. In post-natal sensory neurons, quantitative RT-PCR showed that NKCC1, KCC1 and KCC3 had a higher transcript expression level compared to KCC2 and KCC4. NKCC1 was the main cation-Cl(-) cotransporter controlling Cl(-) accumulation at this developmental stage. In adulthood, the KCC3 transcript was produced in larger amounts than the other cation-Cl(-) cotransporter transcripts and RT-PCR shows larger expression of the shorter KCC3a isoform in adult DRG. Pharmacological inhibitors of cation-Cl(-) cotransporters and the use of KCC3(-/-) mice demonstrated that NKCC1 sustained Cl(-) accumulation in the majority of adult sensory neurons while KCC3 contributed to Cl(-) extrusion in a subset of these neurons. Beta-galactosidase detection in adult KCC3(-/-) DRG showed that KCC3 transcripts were present in all adult sensory neurons suggesting a KCC3 isoform specific regulation of Cl(-) handling. The contribution of KCC3 to Cl(-) extrusion in a subset of sensory neurons indicates that KCC3 could play a major role in GABAergic/glycinergic transmission.
Mol Cell Neurosci 2012 Jul
PMID:KCC3-dependent chloride extrusion in adult sensory neurons. 2260 94


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