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At least 1,531 records · Page 85Linked to original sources
PubMed2003

Electrostatic interaction of pi-acidic amides with hydrogen-bond acceptors.

Interactions between N-methylacetamide (NMA) and N-methylated derivatives of uracil, isocyanurate and barbituric acid have been studied using ab initio methods at the local MP2/6-31G** level of theory. The results were compared to similar interactions between the oxygen atom of NMA and the pi-clouds of perfluorobenzene, quinone and trimethyltriazine. The pi-acidic amides of isocyanurate and barbituric acid were found to interact with a hydrogen bond acceptor primarily through electrostatic attractions. These groups may be used as alternatives of a hydrogen bond donor to complement a hydrogen bond acceptor or an anion in molecular recognition and drug design. Examples of such interactions were identified through a search of the CSD database.

Amides↗
PubMed1999

Correlation of anti-HIV activity with structure: use of electrostatic potential and conformational analysis.

Electrostatic potential distribution, 3-D electron density shapes, and conformational analysis were used to correlate anti-HIV activity or inactivity of AZT, (-) carbovir, oxetanocin A, and 16 isomeric dideoxynucleosides of different families. The structure-activity profile discovered is significant and is expected to contribute to the development of a much needed predictive QSAR analysis in this area.

Adenine↗
PubMed1996

Electrostatic control of GTP and GDP binding in the oncoprotein p21ras.

BACKGROUND: p21ras is one of the GTP-binding proteins that act as intercellular molecular switches. The GTP-bound form of p21ras sends a growth-promoting signal that is terminated once the protein is cycled back into its GDP-bound form. The interaction of guanine-nucleotide-exchange factors (GEFs) with p21ras leads to activation of the protein by promoting GDP --> GTP exchange. Oncogenic mutations of p21ras trap the protein in its biological active GTP-bound form. Other mutations interfere with the activity of GEF. Thus, it is important to explore the structural basis for the action of different mutations. RESULTS: The crystal structures of p21ras are correlated with the binding affinities of GTP and GDP by calculating the relevant electrostatic energies. It is demonstrated that such calculations can provide a road map to the location of 'hot' residues whose mutations are likely to change functional properties of the protein. Furthermore, calculations of the effect of specific mutations on GTP and GDP binding are consistent with those observed. This helps to analyze and locate functionally important parts of the protein. CONCLUSIONS: Our calculations indicate that the protein main chain provides a major contribution to the binding energies of nucleotides and probably plays a key role in relaying the effect of GEF action. Analysis of p21ras mutations in residues that are important for the proper function of GEFs suggests that the region comprising residues 62-67 in p21ras is the major GEF-binding site. This analysis and our computer simulations indicate that the effect of GEF is probably propagated to the P-loop (residues 10-17) through interaction between Gly60 and Gly12. This then reduces the interaction between the main-chain dipoles of the P-loop and the nucleotide. Finally, the results also suggest a possible relationship between the GTP --> GDP structural transition and the catalytic effect of the GTPase-activating protein.

Binding Sites↗
PubMed1999

A dimeric ternary complex of FGFR [correction of FGFR1], heparin and FGF-1 leads to an 'electrostatic sandwich' model for heparin binding.

BACKGROUND: Fibroblastic growth factors (FGFs) are a family of cytokines involved in regulation of cell growth, differentiation and chemotaxis in a variety of tissue types. High-affinity FGF receptors (FGFRs) are transmembrane proteins that consist of three extracellular immunoglobulin-like domains, a transmembrane helix and an intracellular protein tyrosine kinase signalling domain. FGFRs are activated through ligand-dependent dimerization that allows trans-autophosphorylation of the tyrosine kinase domains. Heparin or heparin-like molecules, such as heparan sulphate proteoglycans, bind to both FGFs and FGFRs and are required for FGF signal transduction. At present no structure of the ternary complex for FGFR, FGF and heparin exists. RESULTS: We have used the type-1 interleukin-1 receptor-interleukin-1 beta complex crystal structure, in which both the ligand and the receptor are homologous to those of the FGF-FGFR pair, to identify potential interactions in the FGFR-heparin-FGF ternary complex. A key feature of the modelled complex is the 'electrostatic sandwich' that is formed between the positively charged surfaces of FGF and the receptor, with the negatively charged heparin captured in between. The ternary complex places limits on the range of likely modes of receptor dimerization: one of five different dimeric receptor complexes built from the ternary complex correlates best with the experimental data. CONCLUSIONS: The ternary complex of FGFR, FGF and heparin, derived on the basis of the homologous interleukin-1 receptor complex, is in agreement with much of the published experimental data, as is the dimeric receptor complex (FGFR-heparin-FGF)2. This work suggests that the FGF interactions seen in crystal structures, which have previously been used to predict the mode of FGF dimerization, might not be relevant to the biologically active dimeric FGFR-heparin-FGF complex.

Algorithms↗
PubMed2001

The influence of electrostatic interactions on the detection of heme-globin complexes in ESI-MS.

The heme-globin complexes of hemoglobin and myoglobin are investigated in positive-ion mode and negative-ion mode using a nano-ESI source coupled to a quadrupole ion trap MS and an orthogonal time-of-flight MS. The extent of dissociation of these noncovalent complexes upon collisional activation and thus their gas-phase stability is strongly dependent on the polarity of the ESI-MS experiment as well as on the charge of the prosthetic group (ferri-heme [Fe3+-heme]+ vs. ferro-heme [Fe2+-heme]+/-0). The results clearly point to the important role of electrostatic interactions on the gas phase stability of noncovalent complexes and therefore the ion signals observed in ESI-MS experiments.

Animals↗
PubMed2001

Complexes of Li atoms with formaldehyde (LiOCH2) and formaldimine (LiNHCH2): stability via electrostatic and charge transfer interactions.

The Li atom adducts of formaldehyde (LiOCH2) and formaldimine (LiNHCH2) are produced in the gas phase by neutralization of the corresponding cations. Subsequent reionization, ca. 0.3 micros later, shows that the nominally hypervalent complexes LiXCH2 (X=O or NH) are stable, residing in potential energy minima. In the time span between the neutralization and reionization events, the LiXCH2 molecules dissociate partly into their constituents, Li + XCH2, the fragmentation extent of LiNHCH2 being more extensive. Ab initio calculations reveal three bound states for both Li atom complexes. Two (states A and B) resemble C-centered radicals carrying an ion pair, Li+*(-)X-CH2*, and can be viewed as lithiated derivatives of the hydroxymethyl (HOCH2*) or aminomethyl (H2NCH2*) radical; the third state (C) represents a conventional, electrostatically bonded Li-X=CH2 complex with an essentially intact X=C double bond and the unpaired electron located at the metal atom. States A and B are bound more strongly than state C for LiOCH2; the opposite is true for LiNHCH2, where C is the most stable arrangement and B only marginally bound. The larger degree of dissociation observed for LiNHCH2 vis à vis LiOCH2 upon neutralization-reionization points out that the experiment samples a considerable amount of state B which is barely bound for LiNHCH2.

Journal Article↗
PubMed1997

External and internal electrostatic potentials of cholinesterase models.

The electrostatic potentials for the three-dimensional structures of cholinesterases from various species were calculated, using the Delphi algorithm, on the basis of the Poisson-Boltzmann equation. We used structures for Torpedo californica and mouse acetylcholinesterase, and built homology models of the human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and human butyrylcholinesterase. All these structures reveal a negative external surface potential, in the area around the entrance to the active-site gorge, that becomes more negative as the rim of the gorge is approached. Moreover, in all cases, the potential becomes increasingly more negative along the central axis running down the gorge, and is largest at the base of the gorge, near the active site. Ten key acidic residues conserved in the sequence alignments of AChE from various species, both in the surface area near the entrance of the active-site gorge and at its base, appear to be primarily responsible for these potentials. The potentials are highly correlated among the structures examined, down to sequence identities as low as 35%. This indicates that they are a conserved property of the cholinesterase family, could serve to attract the positively charged substrate into and down the gorge to the active site, and may play other roles important for cholinesterase function.

Amino Acid Sequence↗
PubMed2004

Carbon nanotube electrostatic biprism: principle of operation and proof of concept.

During in situ transmission electron microscopy (TEM) field emission experiments, carbon nanotubes are observed to strongly diffract the imaging TEM electron beam. We demonstrate that this effect is identical to that of a standard electrostatic biprism. We also demonstrate that the nanotube biprism can be used to capture electron-holographic information.

Journal Article↗
PubMed2000

Fourier transform time-of-flight mass spectrometry in an electrostatic ion beam trap

We report on the application of an electrostatic ion beam trap as a mass spectrometer. The instrument is analogous to an optical resonator; ions are trapped between focusing mirrors. The storage time is limited by the residual gas pressure and reaches up to several seconds, resulting in long ion flight paths. The oscillation of ion bunches between the mirrors is monitored by nondestructive image charge detection in a field-free region and mass spectra are obtained via Fourier transform. The principle of operation is demonstrated by measuring the mass spectrum of trapped Ar+ and Xe+ particles, produced by a standard electron impact ion source. Also, mass spectra of heavier PEGnNa+ and bradykinin ions from a pulsed MALDI ion source were obtained. The long ion flight path, combined with mass-independent charge detection, makes this system particularly interesting for the investigation of large molecules.

Journal Article↗
PubMed1993

Investigation of a "screened" electrostatic ion trap for analysis of high mass molecules by fourier transform mass spectrometry.

With the recent adaptation of matrix-assisted laser desorption/ionization (MALDI) of large biomolecules and polymers to Fourier transform mass spectrometric analysis, it is of interest to explore the possible advantages of using a "screened" electrostatic ion trapping technique. It is demonstrated that the observed rate of change of ion cyclotron resonance frequency with trapping potential is in excellent agreement with theory, being independent of mass and charge, in the mass range from 1185 to just under 17,000 Da. When a screened cubic trap is used in a ca. 7-T magnetic field, the electrical potential within the trap is effectively reduced, and ion cyclotron resonance frequency shifts as a function of trapping potential are decreased by a factor of 25. There is no evidence of significant improvement in mass resolution with this trap design, except when higher trapping potentials are compared. In a 9.7-V screened trap measurement, a bovine insulin spectrum with an average resolution of 10,000 is obtained. Comparable mass resolution under conventional trapping conditions could not be obtained for trapping potentials greater than 1.2 V. It is evident from this study that use of the screened trap technique could offer advantages for MALDI-Fourier transform mass spectrometry.

Fourier Analysis↗
PubMed2005

Stable permanently hydrophilic protein-resistant thin-film coatings on poly(dimethylsiloxane) substrates by electrostatic self-assembly and chemical cross-linking.

Poly(dimethylsiloxane) (PDMS) is a biomaterial that presents serious surface instability characterized by hydrophobicity recovery. Permanently hydrophilic PDMS surfaces were created using electrostatic self-assembly of polyethyleneimine and poly(acrylic acid) on top of a hydrolyzed poly(styrene-alt-maleic anhydride) base layer adsorbed on PDMS. Cross-linking of the polyelectrolyte multilayers (PEMS) by carbodiimide coupling and covalent attachment of poly(ethylene glycol) (PEG) chains to the PEMS produced stable, hydrophilic, protein-resistant coatings, which resisted hydrophobicity recovery in air. Attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy revealed that the thin films had excellent chemical stability and resisted hydrophobicity recovery in air over 77 days of measurement. The spectra also showed a dense coverage for PEG dialdehyde and excellent resistance to protein adsorption from undiluted rat serum. Atomic force microscopy revealed dense coverage with PEG dialdehyde and PEG diamine. Contact angle measurements showed that all films were hydrophilic and that the PEG dialdehyde-topped thin film had a virtually constant contact angle (approximately 20 degrees ) over the five months of the study. Electrokinetic analysis of the coatings in microchannels always exposed to air also gave good protein separation and constant electroosmotic flow during the five months that the measurements were done. We expect that the stable, hydrophilic, protein-resistant thin-film coatings will be useful for many applications that require long-term surface stability.

Animals↗
PubMed1999

Electrostatic immobilization of glucose oxidase in a weak acid, polyelectrolyte hyperbranched ultrathin film on gold: fabrication, characterization, and enzymatic activity.

In this paper we show that hyperbranched polymers can be used as a host matrix for electrostatic entrapment of enzymes. Specifically, amine-functionalized glucose oxidase (GOx+) and horseradish peroxidase, as well as poly(amidoamine) dendrimer-modified horseradish peroxidase, reversibly sorb into polyanionic, hyperbranched poly(sodium acrylate) (PAA-) films that are on the order of a few hundred angstroms thick. The quantity of GOx+ entrapped within the PAA- films depends on the nature of film preparation but is typically on the order of 0.06 unit/cm2. The extent to which entrapped GOx+ retains its activity depends on the film history, but for PAA-/GOx+ composites not exposed to glucose and stored at 4 degrees C, the original activity is retained for up to 68 days and perhaps longer.

Acrylates↗
PubMed2000

Electrostatic axially harmonic orbital trapping: a high-performance technique of mass analysis

This work describes a new type of mass analyzer which employs trapping in an electrostatic field. The potential distribution of the field can be represented as a combination of quadrupole and logarithmic potentials. In the absence of any magnetic or rf fields, ion stability is achieved only due to ions orbiting around an axial electrode. Orbiting ions also perform harmonic oscillations along the electrode with frequency proportional to (m/z)-1/2. These oscillations are detected using image current detection and are transformed into mass spectra using fast FT, similarly to FTICR. Practical aspects of the trap design are presented. High-mass resolution up to 150,000 for ions produced by laser ablation has been demonstrated, along with high-energy acceptance and wide mass range.

Journal Article↗
PubMedDate not supplied

Electrostatically driven immobilization of peptides onto (Maleic anhydride-alt-methyl vinyl ether) copolymers in aqueous media.

The covalent immobilization of a model peptide onto the MAMVE copolymer, via the formation of amide bonds, occurred in moderate yields in aqueous conditions. The improvement of the grafting reaction was achieved by adding at the amino terminus of the model peptide a sequence (tag) of three positively charged amino acids, lysine or arginine, and by taking profit of electrostatic attractive interactions between the negatively charged copolymer and the tagged peptides. The arginine tag was more efficient than the lysine tag for enhancing the immobilization reaction, proving that the effect was due to an electrostic driving force. On the basis of these results, a tentative mechanism is discussed, and Scatchard plots pointed out two regimes of binding. With the first, at low polymer load (up to 50% of saturation for a lysine tag and 60-70% for an arginine tag), the binding occurred with a positive cooperative effect, the already bound peptide participating to the binding of others. A second one for higher coverages, for which the binding occurred with a negative cooperativity, and saturation was reached in the presence of a large excess of peptide.

Amino Acid Sequence↗
PubMed1995

Modification of the electrostatic environment is tolerated in the oxyanion hole of the cysteine protease papain.

The oxyanion hole in cysteine and serine proteases can be viewed as an arrangement of prealigned dipoles that complements the changes in charge distribution during the enzymatic reaction. Because of the electrostatic nature of the interaction involved in the oxyanion hole, the introduction of charged residues in that region could have a major effect on the catalytic properties of the enzyme. In this study, residue Gln19, which contributes to one of the hydrogen bonds in the oxyanion hole of papain, has been replaced by glutamic acid, histidine, and asparagine residues. These mutations result in 65-315-fold decreases in kcat/KM, supporting our previous finding that the side chain of Gln19 contributes to transition state stabilization in the oxyanion hole of papain (Ménard et al., 1991a). Since papain is active over a wide range of pH values, the influence of side chain ionization on activity could be measured quantitatively with the mutant Gln19Glu. The pH dependency of kcat/KM for Gln19Glu is not of the classical bell-shaped form normally observed for papain, but instead is modulated by ionization of the Glu19 side chain with a pKa of 6.02. The Gln19Glu mutant at low pH, where the Glu19 side chain is neutral, is the enzyme that displays activity closest to that of wild-type enzyme, with a (kcat/KM)1lim value only 20-fold lower than that for papain. As expected, the activity of the Gln19Glu mutant decreases when the Glu19 side chain ionizes. However, introduction of the negatively charged glutamate into the oxyanion hole of papain leads to a further reduction in activity of only 12-fold, and this mutant is still more active than the Gln19Ser enzyme and only 3-fold less active than Gln19Asn.(ABSTRACT TRUNCATED AT 250 WORDS)

Anions↗
PubMed1995

Electrostatic dominoes: long distance propagation of mutational effects in photosynthetic reaction centers of Rhodobacter capsulatus.

Two point mutants from the purple bacterium Rhodobacter capsulatus, both modified in the M protein of the photosynthetic reaction center, have been studied by flash-induced absorbance spectroscopy. These strains carry either the M231Arg --> Leu or M43ASN --> Asp mutations, which are located 9 and 15 A, respectively, from the terminal electron acceptor QB. In the wild-type Rb. sphaeroides structure, M231Arg is involved in a conserved salt bridge with H125Glu and H232Glu and M43Asn is located among several polar residues that form or surround the QB binding site. These substitutions were originally uncovered in phenotypic revertants isolated from the photosynthetically incompetent L212Glu-L213Asp --> Ala-Ala site-specific double mutant. As second-site suppressor mutations, they have been shown to restore the proton transfer function that is interrupted in the L212Ala-L213Ala double mutant. The electrostatic effects that are induced in reaction centers by the M231Arg --> Leu and M43Asn --> Asp substitutions are roughly the same in either the double-mutant or wild-type backgrounds. In a reaction center that is otherwise wild type in sequence, they decrease the free energy gap between the QA- and QB- states by 24 +/- 5 and 45 +/- 5 meV, respectively. The pH dependences of K2, the QA-QB <--> QAQB- equilibrium constant, are altered in reaction centers that carry either of these substitutions, revealing differences in the pKas of titratable groups compared to the wild type.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Electrostatic guidance of catalysis by a conserved glutamic acid in Escherichia coli dTMP synthase and bacteriophage T4 dCMP hydroxymethylase.

Thymidylate synthase (TS) and dCMP hydroxymethylase (CH) are homologous enzymes which catalyze the alkylation of C5 of pyrimidine nucleotides. One of the first catalytic steps is isomerization of the alkyl donor, methylenetetrahydrofolate, from its N5,N10 bridged form to the N5 iminium ion upon enzyme binding. Glu58 in TS has been postulated [Matthews et al. (1990) J. Mol. Biol. 214, 937-948] to be involved in this isomerization and the deprotonation of C5 of the nucleotide. Substitution by Asp or Gln of Glu58 in Escherichia coli TS, or of the corresponding Glu60 in CH from phage T4, decreases the activity of either enzyme. Alkylation is slowed much more than deprotonation, indicating uncoupling of steps which are tightly coupled for the wild-type enzymes. The data support minor roles for Glu58/60 in nucleotide binding and in isomerization of methylenetetrahydrofolate, but no major roles in nucleotide deprotonation, product dissociation, or hydration catalyzed by CH. The primary role of Glu58/60 is to accelerate bond cleavage between N5 of tetrahydrofolate and the methylene being transferred. The influence of Glu58/60 on the rate of bond cleavage is proposed to arise from electrostatic destabilization due to the proximity of the glutamyl carboxylate, of the anionic species formed when C5 of the nucleotide is deprotonated. The proposal explains the uncoupling of deprotonation and alkylation with the Glu58/60 variants and the reduced kinetic isotope effect on hydride transfer for TS(Glu58Gln). The inability of 5-deazatetrahydrofolate to stimulate enzyme-catalyzed tritium exchange from [5-(3H)]nucleotides into solvent suggests that N5 of tetrahydrofolate is the base which deprotonates the nucleotide.

Amino Acid Sequence↗