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At least 433 records · Page 24Linked to original sources
PubMed1999

Electrostatic effects on the kinetics of photoinduced electron-transfer reactions of the triplet state of zinc cytochrome c with wild-type and mutant forms of Pseudomonas aeruginosa azurin.

We study, by laser flash photolysis, the effects of ionic strength on the kinetics of the reaction 3Zncyt + az(II)-->Zncyt+ + az(I), i.e., oxidative quenching of the triplet state of zinc cytochrome c by the wild-type form and the following three mutants of cupriazurin: Met44Lys, Met64Glu, and the double mutant Met44Lys/Met64Glu. Mutations in the hydrophobic patch of azurin significantly affect the reactivity of the protein with the triplet state of zinc cytochrome c. Dependence on the ionic strength of the bimolecular rate constant for the aforementioned reaction is analyzed by several electrostatic models. The two transition-state theories, Brønsted-Debye-Hückel and van Leeuwen theories, allow the best approximation to the experimental data when effective charges of the proteins are used. Protein-protein interactions are also analyzed in terms of local charges on the protein surfaces. The rate constants depend little on ionic strength, and the monopolar and dipolar electrostatic interactions between zinc cytochrome c and azurin are not well resolved. Semiquantitative analysis of electrostatic interactions indicates that azurin uses its hydrophobic patch for contact with zinc cytochrome c.

Azurin↗
PubMed2003

Molecular dynamics simulation of hepatitis C virus IRES IIId domain: structural behavior, electrostatic and energetic analysis.

The dynamic behavior of the HCV IRES IIId domain is analyzed by means of a 2.6-ns molecular dynamics simulation, starting from an NMR structure. The simulation is carried out in explicit water with Na+ counterions, and particle-mesh Ewald summation is used for the electrostatic interactions. In this work, we analyze selected patterns of the helix that are crucial for IRES activity and that could be considered as targets for the intervention of inhibitors, such as the hexanucleotide terminal loop (more particularly its three consecutive guanines) and the loop-E motif. The simulation has allowed us to analyze the dynamics of the loop substructure and has revealed a behavior among the guanine bases that might explain the different role of the third guanine of the GGG triplet upon molecular recognition. The accessibility of the loop-E motif and the loop major and minor groove is also examined, as well as the effect of Na+ or Mg2+ counterion within the simulation. The electrostatic analysis reveals several ion pockets, not discussed in the experimental structure. The positions of these ions are useful for locating specific electrostatic recognition sites for potential inhibitor binding.

Amino Acid Motifs↗
PubMed2006

Force-field parametrization of retro-inverso modified residues: development of torsional and electrostatic parameters.

Torsional and the electrostatic parameters for molecular mechanics studies of retro-inverso modified peptides have been developed using quantum mechanical calculations. The resulting parameters have been compared with those calculated for conventional peptides. Rotational profiles, which were obtained spanning the corresponding dihedral angle, were corrected by removing the energy contributions associated to changes in interactions different from torsion under study. For this purpose, the torsional energy associated to each point of the profiles was estimated as the corresponding quantum mechanical energy minus the bonding and nonbonding energy contributions produced by the perturbations that the variation of the spanned dihedral angle causes in the bond distances, bond angles and the other dihedral angles. These energies were calculated using force-field expressions. The corrected profiles were fitted to a three-term Fourier expansion to derive the torsional parameters. Atomic charges for retro-inverso modified residues were derived from the rigorously calculated quantum mechanical electrostatic potential. Furthermore, the reliability of electrostatic models based on geometry-dependent charges and fixed charges has been examined.

Amino Acids↗
PubMed1990

Comparison of the kinetics of reduction and intramolecular electron transfer in electrostatic and covalent complexes of ferredoxin-NADP+ reductase and flavodoxin from Anabaena PCC 7119.

The kinetics of reduction and intracomplex electron transfer in electrostatically stabilized and covalently crosslinked complexes between ferredoxin-NADP+ reductase (FNR) and flavodoxin (Fld) from the cyanobacterium Anabaena PCC 7119 were compared using laser flash photolysis. The second-order rate constant for reduction by 5-deazariboflavin semiquinone (dRfH) of FNR within the electrostatically stabilized complex at 10 mM ionic strength (4.0 X 10(8) M-1 s-1) was identical to that for free FNR. This suggests that the FAD cofactor of FNR is not sterically hindered upon complex formation. A lower limit of approximately 7000 s-1 was estimated for the first-order rate constant for intracomplex electron transfer from FNRred to Fldox under these conditions. In contrast, for the covalently crosslinked complex, a smaller second-order rate constant (2.1 X 10(8) M-1 s-1) was obtained for the reduction of FNR by dRfH within the complex, suggesting that some steric hindrance of the FAD cofactor of FNR occurs due to crosslinking. A limiting rate constant of 1000 s-1 for the intracomplex electron transfer reaction was obtained for the covalent complex, which was unaffected by changes in ionic strength. The substantially diminished limiting rate constant, relative to that of the electrostatic complex, may reflect either a suboptimal orientation of the redox cofactors within the covalent complex or a required structural reorganization preceding electron transfer which is not allowed once the proteins have been covalently linked. Thus, although the covalent complex is biochemically competent, it is not a quantitatively precise model for the catalytically relevant intermediate along the reaction pathway.

Cyanobacteria↗
PubMed1990

Electrostatic control of charge separation in bacterial photosynthesis.

Electrostatic interaction energies of the electron carriers with their surroundings in a photosynthetic bacterial reaction center are calculated. The calculations are based on the detailed crystal structure of reaction centers from Rhodopseu-domonas viridis, and use an iterative, self-consistent procedure to evaluate the effects of induced dipoles in the protein and the surrounding membrane. To obtain the free energies of radical-pair states, the calculated electrostatic interaction energies are combined with the experimentally measured midpoint redox potentials of the electron carriers and of bacteriochlorophyll (BChl) and bacteriopheophytin (BPh) in vitro. The P+HL- radical-pair, in which an electron has moved from the primary electron donor (P) to a BPh on the 'L' side of the reaction center (HL), is found to lie approx. 2.0 kcal/mol below the lowest excited singlet state (P*), when the radical-pair is formed in the static crystallographic structure. The reorganization energy for the subsequent relaxation of P+HL- is calculated to be 5.0 kcal/mol, so that the relaxed radical-pair lies about 7 kcal/mol below P*. The unrelaxed P+BL- radical-pair, in which the electron acceptor is the accessory BChl located between P and HL, appears to be essentially isoenergetic with P*.P+BM-, in which an electron moves to the BChl on the 'M' side, is calculated to lie about 5.5 kcal/mol above P*. These results have an estimated error range of +/- 2.5 kcal/mol. They are shown to be relatively insensitive to various details of the model, including the charge distribution in P+, the atomic charges used for the amino acid residues, the boundaries of the structural region that is considered microscopically and the treatments of the histidyl ligands of P and of potentially ionizable amino acids. The calculated free energies are consistent with rapid electron transfer from P* to HL by way of BL, and with a much slower electron transfer to the pigments on the M side. Tyrosine M208 appears to play a particularly important role in lowering the energy of P+BL-. Electrostatic interactions with the protein favor localization of the positive charge of P+ on PM, one of the two BChl molecules that make up the electron donor.

Bacterial Proteins↗
PubMed1983

Electrostatic control by lipids upon the membrane-bound (Na+ + K+)-ATPase. II. The influence of surface potential upon the activating ion equilibria.

Electrostatic influences upon the enzymatic activity of the (Na+ + K+)-ATPase from ox brain (EC 3.6.1.3) have been studied. (1) The characteristics of the temperature dependence of the activity - the slopes and inflection temperature, Ti, of the Arrhenius plots - have been shown to depend on the total concentration, but not on the specific properties of added monovalent ions. (2) The enzymatic activity has been shown to be subject simultaneously to unspecific and specific influences of alkali-metal ions or NH+4. Ion-specific effects result from different binding constants of complexation between activating ions and enzyme. These stability constants are affected by the formation of an electrical double layer at the membrane surface. With increasing electrostatic screening, the complex formation is destabilized and, as a consequence, the enzymatic activity decreases. (3) This interaction between ion binding and surface electrostatics enables the enzyme to adapt its activity to the actual ionic conditions. This gives rise to a complex net dependence of the enzymatic activity upon the concentrations of activating ions. Such dependencies are analyzed, and an 'activity surface' has been constructed which represents the enzymatic activity as a function of simultaneously varying concentrations of sodium and potassium. The shape of this activity surface is determined by the relations between ion concentrations, surface potential and the resulting stability of the complexation between the activating ions and the enzyme. By means of three-dimensional representation it is demonstrated that the adaptability of the stability constants is of great importance with respect to the maintenance of the optimal ionic concentrations within the living cell. Therefore, by means of the surrounding membrane, the ATPase is provided with a quality, in addition to its substrate specificity and catalytic ability, which is necessary for its function as a transport enzyme.

Animals↗
PubMed1978

Electrostatic complexes of mitomycin C with nucleic acids and polyanions.

Reductively activated mitomycin C exhibits strong, non-covalent electrostatic binding to polyanions such as polyvinylsulfate and polyphosphate. The protonated C-2 amino group generated by the reduction is most likely responsible for this type of interaction. At moderate drug and salt concentrations only covalent binding to nucleic acids is observable. This is shown to be guanine-specific in DNA for the first time, as well as in synthetic polyribo- and polydeoxyribonucleotides at 10--20 times higher binding levels than previously tested. At higher mitomycin C concentration, however, strong non-covalent electrostatic binding to nucleic acids also occurs, resulting in a binding ratio up to 1 mol drug bound per mol mononucleotide, although this non-specific binding is relatively inhibited compared to polyvinylsulfate. Salts also have an inhibitory effect on the non-specific binding to nucleic acids. A series of mitomycin derivatives were compared for their binding and cross-linking abilities using DNA as substrate, with the following results: (a) the presence of a basic nitrogen . funtion at C-2 promotes binding, both covalent and electrostatic, presumably by kinetically facilitating the approach between positively charged nitrogen and DNA. (b) The aziridine ring is the major covalent binding site, indispensable for crosslinking and determines the guanine-specificity of the binding.

Anions↗
PubMed1989

An alpha-helical peptide model for electrostatic interactions of proteins with DNA. The N terminus of RecA.

A series of synthetic peptides have been studied as models for non-specific protein-DNA interactions. In an alpha-helical conformation, the charged amino acid residues of the N-terminal 24 residues of RecA protein are asymmetrically distributed; at neutral pH there is a +4 charge on one face of the helix and a -3 charge on the other face. Modeling suggests that the positive face of the helix can bind five DNA phosphate groups by electrostatic interactions. Circular dichroism (c.d.) spectra indicate that the analogous peptide, Rec24 (AIDENKQKALAAALGQIEKQFGKG-amide), is largely unstructured in water but becomes highly helical in the presence of DNA. Peptide titrations of fluorescent etheno-DNA confirm that the changes in the c.d. spectrum of the peptide are associated with binding, although a dependence of the c.d. signal on the degree of DNA saturation is observed, indicating that peptide can be bound in more than one conformation. At saturation the peptide binds to 5.0(+/- 0.5) DNA phosphate groups as predicted and the electrostatic nature of the binding is confirmed by a strong dependence on salt concentration. A "mutant" peptide where an acidic glutamate residue replaces an alanine on the basic face of the Rec24 helix exhibits weaker binding to single-stranded DNA, also consistent with the electrostatic nature of the proposed peptide-DNA interaction. Extending Rec24 by ten amino acid residues, where the additional residues do not participate in the helical motif, does not noticeably affect binding. Thus, we show experimentally that an asymmetric charge distribution on an alpha-helix can represent an important element for binding nucleic acids.

Alanine↗
PubMed1989

Investigating protein-protein interaction surfaces using a reduced stereochemical and electrostatic model.

A method of calculating the electrostatic potential energy between two molecules, using finite difference potential, is presented. A reduced charge set is used so that the interaction energy can be calculated as the two static molecules explore their full six-dimensional configurational space. The energies are contoured over surfaces fixed to each molecule with an interactive computer graphics program. For two crystal structures (trypsin-trypsin inhibitor and anti-lysozyme Fab-lysozyme), it is found that the complex corresponds to highly favourable interacting regions in the contour plots. These matches arise from a small number of protruding basic residues interacting with enhanced negative potential in each case. The redox pair cytochrome c peroxidase-cytochrome c exhibits an extensive favourably interacting surface within which a possible electron transfer complex may be defined by an increased electrostatic complementarity, but a decreased electrostatic energy. A possible substrate transfer configuration for the glycolytic enzyme pair glyceraldehyde phosphate dehydrogenase-phosphoglycerate kinase is presented.

Animals↗
PubMed1991

Cumulative site-directed charge-change replacements in bacteriophage T4 lysozyme suggest that long-range electrostatic interactions contribute little to protein stability.

Bacteriophage T4 lysozyme is a basic molecule with an isoelectric point above 9.0, and an excess of nine positive charges at neutral pH. It might be expected that it would be energetically costly to bring these out-of-balance charges from the extended, unfolded, form of the protein into the compact folded state. To determine the contribution of such long-range electrostatic interactions to the stability of the protein, five positively charged surface residues, Lys16, Arg119, Lys135, Lys147 and Arg154, were individually replaced with glutamic acid. Eight selected double, triple and quadruple mutants were also constructed so as to sequentially reduce the out-of-balance formal charge on the molecule from +9 to +1 units. Each of the five single variant proteins was crystallized and high-resolution X-ray analysis confirmed that each mutant structure was, in general, very similar to the wild-type. In the case of R154E, however, the Arg154 to Glu replacement caused a rearrangement in which Asp127 replaced Glu128 as the capping residue of a nearby alpha-helix. The thermal stabilities of all 13 variant proteins were found to be fairly similar, ranging from 0.5 kcal/mol more stable than wild-type to 1.7 kcal/mol less stable than wild-type. In the case of the five single charge-change variants, for which the structures were determined, the changes in stability can be rationalized in terms of changes in local interactions at the site of the replacement. There is no evidence that the reduction in the out-of-balance charge on the molecule increases the stability of the folded relative to the unfolded form, either at pH 2.8 or at pH 5.3. This indicates that long-range electrostatic interactions between the substituted amino acid residues and other charged groups on the surface of the molecule are weak or non-existent. Furthermore, the relative stabilities of the multiple charge replacement mutant proteins were found to be almost exactly equal to the sums of the relative stabilities of the constituent single mutant proteins. This also clearly indicates that the electrostatic interactions between the replaced charges are negligibly small. The activities of the charge-change mutant lysozymes, as measured by the rate of hydrolysis of cell wall suspensions, are essentially equal to that of the wild-type lysozyme, but on a lysoplate assay the mutant enzymes appear to have higher activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Arginine↗
PubMed1983

Comparison of protein electrostatic potential along the catalytic triad of serine proteinases.

Intraproteic electrostatic potentials along the catalytic triad in serine proteinases are compared for eight enzymes for which three-dimensional co-ordinates are available. We used our bond-increment method to calculate the potential and we considered all protein atoms, including hydrogens. It was found that counter ions which may be located in the vicinity of charged surface side chains play a decisive role in determining enzymatic action. If ionizable side chains are neutralized the electrostatic potential curve across the catalytic triad is of minimum character in all investigated enzymes. It stabilizes the (-+-) charge distribution which models the Ser- -His+ -Asp- transition state structure which is formed during the catalytic process. Based on the close similarity of the electrostatic pattern in various enzymes we call attention to the possibility that convergent evolution produced not only the effective catalytic triad but also a minimum-type potential which accelerates the enzymatic reaction.

Amino Acid Sequence↗
PubMed1983

A biophysical model for interaction of cells with a surface coat (glycocalyx). I. Electrostatic interaction profile.

A model of the primary stage of cell-cell interaction is assumed, including not only the classical electrostatic and electrodynamic energies in the sense of DLVO theory but also steric interaction energy, the energy of specific and non-specific bonds and the energy due to changes of surface potential. Furthermore, in this paper, we exploit recent advances in the understanding of the structure of the cell surface (glycocalyx), assuming the fixed electrostatic charges (dissociated groups of the glycocalyx), to be space charge densities and the glycocalyx itself to be an adsorption layer. In this first part the profile of the electrostatic potential between two cells is calculated on the basis of the linear Poisson-Boltzmann equation (analytical integration) and discussed in dependence on charge densities of the glycocalyx, the separation distance between cells and the ionic strength of the suspension medium.

Biophysical Phenomena↗
PubMed1983

Anionic sites in basement membranes. Differences in their electrostatic properties in continuous and fenestrated capillaries.

We have used ruthenium red, a cationic dye, to detect at the electron microscopic level the presence of anionic sites in various murine basement membranes, with particular emphasis on those of the microvasculature. We have observed anionic sites in all continuous and fenestrated capillaries examined. Terminal lymphatics, which have a discontinuous basement membrane, have sites only where the basement membrane is present. Anionic sites are not present beneath sinusoidal lining cells of the liver which lack a basement membrane. Basement membranes of epithelial cells and those surrounding striated and smooth muscle cells, pericytes, fat cells, and Schwann cells also exhibit anionic sites. We compared the electrostatic properties of anionic sites in basement membranes of continuous and fenestrated capillaries by determining the salt concentration (critical electrolyte concentration, Scott and Dorling, 1965) required to displace ruthenium red from the sites. A concentration of 0.5 M Na+ was required to displace ruthenium red from the basement membrane of continuous capillaries of muscle whereas 1.3 M Na+ was required to displace ruthenium red from the basement membrane of fenestrated peritubular capillaries of the renal cortex. Our results suggest that anionic sites in the basement membrane of fenestrated peritubular capillaries are more strongly negatively charged than those in the basement membrane of continuous capillaries of muscle. We conclude from this study, first, that anionic sites are a general property of vascular, epithelial, and pericellular basement membranes and, second, that the electrostatic properties of the sites differ in different vascular basement membranes. We speculate that the anionic sites in vascular basement membranes and the variation in their electrostatic properties in different types of capillaries may have important implications for exchange of substances across the capillary wall.

Animals↗
PubMed1994

The use of molecular graphics and quantum mechanically derived electrostatic potentials to visualize Brönsted acid site strength in zeolites.

The use of the quantum mechanically derived electrostatic potential is introduced to visualize the variation in acidity across a series of cluster molecules corresponding to models of terminal and bridged hydroxyl groups in zeolites. The electrostatic potential is color coded onto the electron density surfaces of the molecules involved, and the variation in acid strength can be followed from the color scheme used. This simple visualization scheme is shown to mirror the experimentally observed acidity variation of terminal hydroxyls, bridged gallium hydroxyls, and bridged aluminium hydroxyls found for zeolites. From the value of the electrostatic potential near the acidic hydrogen we estimate that the acidity of terminal hydroxyls is similar to acetic acid while the bridged aluminium form is the same as sulphuric acid.

Acids↗
PubMed1975

Cation bindint to alpha-sl-casein B. A comparison of electrostatic models.

System characteristics which determine calcium binding to and subsequent proton release from alpha-sl-casein B are reported at pH 6.6 and [Na-plus] equal to 0.04, 0.0, and 0.16M. Values of protein solvation, G, site bound calcium, Ca,S, and net monomer charge, Z, permitted distributed charge models to be constructed. The models examined proved inadequate in that it was impossible to keep the dielectric constant, D, within acceptable limits and/or predict measured proton release. Three discrete charge models were constructed. At D equals 4, all three gave good agreement between predicted and experimental data as Ca, S increased. The known amino acid sequence was used to make rodlet models for the whole molecule andfor just the phosphate-containing acidic peptide portion. A comparison of these shows the electrostatic dominance of the acidic peptide and suggests that the electrostatic environment for the remainder of the binding sites is essentially constant as Ca, S increases during addition of calcium ion. The third discrete charge model bends the acidic peptide rodlet into a torus. In this case, data were matched with less assumed bond strain under conditions of high molecular charge than with the other two models. This indicates that conformation and association may be important factors to consider when constructing discrete charge models to calculate electrostatic free energy.

Amino Acid Sequence↗
PubMed1976

Electrostatic interactions at charged lipid membranes. I. Effects of pH and univalent cations on membrane structure.

Electrostatic interactions at charged lipid membranes make a significant contribution to the free energy of the system, and can be varied within a wide range by alteration either of the membrane's surface charge density or of the concentration of electrolytes in the surrounding medium. Changes in the charged membrane's structure, such as the ordered in equilibrium fluid phase transition, can thus be induced at constant temperature by variations in pH and salt concentration. An adequate quantitative description of these phenomena is obtained from the Gouy--Chapman theory. The good agreement between theory and experiment confirms that the expression derived for the electrostatic free energy especially in respect of its positive sign is correct. The classical expression derived for the electrostatic free energy, especially in respect of its positive sign, is correct. The classical expression for the "free energy of the double layer" derived by Verwey and Overbeek, which has a negative sign, is not applicable to lipid membranes with ionizable polar groups.

Cations, Monovalent↗
PubMed1994

Electrostatic effects in short superhelical DNA.

We present Monte Carlo simulations of the equilibrium configurations of short closed circular DNA that obeys a combined elastic, hard-sphere, and electrostatic energy potential. We employ a B-spline representation to model chain configuration and simulate the effects of salt on chain folding by varying the Debye screening parameter. We obtain global equilibrium configurations of closed circular DNA, with several imposed linking number differences, at two salt concentrations (specifically at the extremes of no added salt and the high salt regime), and for different chain lengths. Minimization of the composite elastic/long-range potential energy under the constraints of ring closure and fixed chain length is found to produce structures that are consistent with the configurations of short supercoiled DNA observed experimentally. The structures generated under the constraints of an electrostatic potential are less compact than those subjected only to an elastic term and a hard-sphere constraint. For a fixed linking number difference greater than a critical value, the interwound structures obtained under the condition of high salt are more compact than those obtained under the condition of no added salt. In the case of no added salt, the electrostatic energy plays a dominant role over the elastic energy in dictating the shape of the closed circular DNA. The DNA supercoil opens up with increasing chain length at low salt concentration. A branched three-leaf rose structure with a fixed linking number difference is higher in energy than the interwound form at both salt concentrations employed here.

DNA, Superhelical↗
PubMed1996

Electrostatic interactions in hirudin-thrombin binding.

Hirudin is a good anticoagulant owing to potent inhibition of the serine protease thrombin. An aspartate- and glutamate-rich portion of hirudin plays an important part in its tight binding to thrombin through a ladder of salt bridges, and these residues have previously been mutated to asparagine or glutamine. Detailed calculations of the electrostatic contribution to changes in binding from these mutations have been performed using the finite-difference Poisson-Boltzmann method which include charge--charge interactions, solvation interactions, the residual electrostatic interaction of mutant residues, pKa shifts, and ionic strength. Single mutant effects on binding energy were close to experimental values, except for the D55N mutant whose effect is overestimated, perhaps because of displacement of a bound chloride ion from the site where it binds. Multiple mutation values were generally overestimated. The effect of pKa shifts upon the binding is significant for one hirudin residue E58, but this appears to be due to a poor salt bridge with thrombin caused by crystal contacts. Electrostatic interaction between the acidic residues is unfavorable. However, analysis of experimental multiple mutation/single mutation data shows apparently negative interactions between these residues, from which it is concluded that structural changes can occur in the complex to relieve an unfavorable interaction when more than one acidic residue is mutated. In all cases, there is a loss in stability of the complex from mutations due to loss of favorable charge--charge interactions with thrombin, but this is largely compensated for by reduced unfavorable desolvation interactions, and by residual polar interactions in the Asn/Gln mutants.

Anticoagulants↗