bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational characteristics of polyglutamic acid esters: Persistence of orientational correlation along the side chain flanking the α‐helical backbone
Authors: Yamazaki Toshimasa , Abe Akihiro , Ono Hirobumi , Toriumi Hirokazu 
Published: December 2004

AbstractThe side chain conformations of α‐helical poly(L‐glutamic acid) esters \documentclass{article}\pagestyle{empty}\begin{document}$ \rlap{--}[NHCH(CH_2 CH_2 COOR)CO\rlap{--}]_x $\end{document}, carrying a homologous series of ester residues such as R = (CH2)nϕ with n = 1–3, have been studied in the lyotropic liquid crystalline state (chloroform 20 v/v%) by the deuterium nmr method. In order to study the surface chirality of the molecule, the phenyl groups situated at the terminal of the side chain have been deuterated. From the observed deuterium quadrupolar splittings, the average inclination θp of the para‐axis of the phenyl group with respect to the α‐helical backbone was elucidated. A distinct odd–even oscillation in the quantity such as 〈 cos2 θp〉 was observed with the number of methylene units n. A rotational isomeric state analysis has indicated that the observed orientational correlation arises from the interdependence of the neighboring bond rotation along the side chain. Preference of the “extended” conformations is also enhanced by the mutual conformational exclusion of neighboring side chains.
Comparative gel electrophoresis measurement of the DNA bend angle induced by the catabolite activator protein
Authors: Zinkel Sandra S. , Crothers Donald M. 
Published: December 2004

AbstractWe describe a method to determine the magnitude of protein‐induced DNA bends relative to a set of standard A tract bends using comparative gel electrophoresis. The DNA bend of interest was that induced by the catabolite activator protein (CAP), the transcriptional activator protein of the lac operon. The set of comparison molecules contained both bends of known magnitude and a bound CAP. The electrophoretic influence of the bound protein was accounted for by placing its binding site at the end of the molecule where its induced bend has little influence. Standard bends at the DNA center were introduced by incorporating 3–9 A6 tracts at ∼ 10.5 base‐pair phasing. The mobility of these control molecules was compared to the mobility of a test molecule of comparable length containing a central CAP‐induced DNA bend. The CAP bend angle was found to be 5.6 ± 0.3 A tract equivalents, or ∼ 100°, independent of the concentration of the gel used within the range tested. The dependence of gel retardation on DNA end‐to‐end distance was found to break down for A tract bend angles above 120°, corresponding roughly to the angle beyond which the long axis of the molecule is no longer parallel to the end‐to‐end vector. We speculate that this may reflect a switch in the mode of migration of molecules through the gel.
Far‐UV CD spectroscopy, IR spectroscopy, and immunological properties of synthetic peptides, including an amphipathic α‐helical peptide from bovine phospholipase A2
Authors: Osthoff Gernot , Nel Alida J. 
Published: December 2004

AbstractThe immunological properties of bovine phospholipase A2 were investigated in order to locate possible sequential epitopes. Polyvalent antiserum raised against the enzyme was tested for its interaction with synthetic peptides derived from regions adopting hydrogen‐bonded secondary structures within the tertiary structure of phospholipase A2. The conformations of each peptide in various solvents were determined by CD and ir spectroscopy in order to relate immunological to structural properties. It was found that sequential epitopes are absent in this enzyme, but that region 90–109 could be a possible T‐cell epitope through the formation of an amphipathic α‐helix.
Assesment of protein reorientational diffusion in solution by 13C off‐resonance rotating frame spin–lattice relaxation: Effect of polydispersity
Authors: Morgan Courtney F. , Schiliech Thomas , Caines G. Herbert 
Published: December 2004

AbstractThe 13C off‐resonance rotating frame spin‐lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in both model in vitro and in vivo systems. The original formalism of James and co‐workers [(1978) J. Am. Chem. Soc. 100, 3590–3594] was constrained by the assumption of random isotropic reorientational motion of a monodisperse protein population. Here we extend the formalism to include polydispersity. Application is made to the alkaline pH induced association of lysozyme, lysozyme–bovine serum albumin mixtures, and to the phase separation of lysozyme salt–water mixtures induced by low temperature.
The influence of Li+, Na+, Mg2+, Ca2+, and Zn2+ ions on the hydrogen bonds of the Watson–Crick base pairs
Authors: Anwander Eugen H. S. , Probst Michael M. , Rode Bernd M. 
Published: December 2004

AbstractThe interaction of mono‐ and divalent metal ions with the nucleic acid base pairs A:T and G:C has been studied using ab initio self‐consistent field Hartree–Fock computations with minimal basis sets. Energy‐optimized structures of the two base pairs with a final base–base distance of L = 10.35 Å have been determined and were further used in calculations on ternary complexes Mn+ – A:B together with previously computed coordination geometries of the cations at adenine (Ade), thymine (Thy), and guanine (Gua). Besides the binding energy of the various metal ions to the base pairs, changes in the stability of the H bonds between Ade and Thy or Gua and Cyt have been determined. Polarization effects of the metal ion on the ligand turned out to increase the binding between complementary bases. Regardless of the metal species, cation binding to Gua N(3) and Thy O(2) leads to a special increase in H‐bond stability, whereas binding to Ade N(3) changes the H‐bond stability least. Situated in between are the stabilizing effects caused by Gua and Ade N(7) coordination. A remarkable relation between the stability of the H bond and the distance from metal binding site to H bonds was found. This relationship has been rationalized in terms of partial charges of the atoms participating in H bonding, which can reveal the trend in the electrostatic part of total H bond energy. It can be shown that a short distance between coordination site and acceptor hydrogen increases the H‐bond strength substantially, while a long distance shows minor effects as supposed. On the other hand, the opposite effect is observed for the influence of the distance between binding site and donor atom. A comparison of our findings with a new model of transition metal ion facilitated rewinding of denatured DNA proposed by S. Miller, D. VanDerveer, and L. Marzilli is given [(1985) J. Am. Chem. Soc. 107, 1048–1055].
Environmental control of reactions: Influence of poly(glutamate) on the reactivity of cysteine‐quaterpyridineiron (III) mixtures
Authors: Paradossi G. , Palleschi A. , Desideri A. , Pispisa B. 
Published: December 2004

AbstractQuaterpyridineiron(III) complex ions (FeT) anchored to ordered poly(L‐glutamate) or poly(D‐glutamate) were used as enantiomeric systems for stereoselective oxidation of L‐cysteine, a widely encountered ligand in both heme and nonheme iron–sulfur proteins. Surprisingly, electron transfer from substrate to the central metal ion does not take place, despite the favorable thermodyamic driving force. Instead, a stable, polymer‐supported, Fe(III)T‐cysteinate complex forms, to which no stereoselectivity is associated. This finding contrasts the known lability of iron(III)–thiolate complexes, ultimately yielding disulfides and iron(II) species, and is relevant in view of the current interest in model compunds of cytochrome P‐450, where cysteine is axially bound to ferric prophyrin. The formation of this complex was studied by kinetics and low‐temperature electron paramagnetic resonance spectroscopy, while the stereochemical features of the diastereomeric encounter intermediates were investigated by theoretical conformational analysis. The results collectively emphasize the environmental contraol of the polypeptide matrix on the stability of cysteinate sulfur axial ligation. Implications of the absence of stereoselectivity in the reaction investigated are also discussed in the light of a few general considerations concerning chiral discrimination in reactions between optically active compounds.
A molecular dynamics simulation of the (dG)6·(dC)6 minihelix including counterions and water
Authors: Zielinski Theresa Julia , Shibata Masayuki 
Published: December 2004

AbstractThe results of a 60 ps molecular dynamics (MD) simulation of (dG)6·(dC)6 including 10 Na+ counterions and 292 water molecules are presented. All backbone angles and helix parameters for the hexamer are reported in this paper along with trajectory plots of selected angles. Hydrogen bonding between the bases along the helical axis was observed to flucturate with time, showing the dynamic nature of the base‐pairing interaction. These fluctuations gave rise to unusual hydrogen‐bonding patterns. Good intrastrad base stacking and no interstrand base stacking were also observed. The hexamer minihelix retains an essentially B‐DNA conformation throughout the entire simulation even though some helix parameters and backbone angles do not have strict B‐DNA values. The most striking feature obtained from the simulation was a high propeller twist, which resulted in a narrow minor groove for the minihelix. It is proposed that (dG)n·(dC)n sequences are resistant to DNAase I because of this narrow minor groove in dilute aqueous solution.
An ellipticine derivative (oxazolopyridocarbazolium) 3′ linked to tetrathymidylate stacks intramolecularly with the nearest thymine at low concentration and head‐to‐tail intermolecularly at high concentration
Authors: Bazile D. , Guittet E. , Piriou J.‐M. , Lebret M. , Paoletti J. 
Published: December 2004

AbstractThe solution conformation of a tetrathymidylate linked through an ester bond to an ellipticine derivative oxazolopyridocarbazolium (OPC) at the 3′ position was investigated using one‐ and two‐dimensional nmr experiments. Since the total electric charge of the OPC ring may influence self‐association, we first determined the pKa of the oxazole cyclic acidic function. Nuclear Overhauser effect spectroscopy experiments showed that, at low concentration, the OPC stacks intramolecularly with the nearest thymine at the 3′ end. At highest concentration, however, the OPC rings are self‐associated. The stacking constant was calculated using 1H chemical shift dilution experiment. The conformational model suggested by P‐nmr was tested by molecular mechanics computations.
The thermodynamics of hydrogen isotope exchange in lysozyme: The influence of glycerol
Authors: Gregory Roger B. , Rosenberg Andreas , Knox Donald , Percy Amy J. 
Published: December 2004

AbstractThe temperature dependence of hydrogen isotope exchange rates for lysozyme in 5 molal aqueous glycerol and for poly (D,L‐alanine) in a range of glycerol concentrations from 0 molal to 8 molal have been determined. The activation enthalpy of base‐catalyzed exchange for poly (D,L‐alanine) in water is 4 kcal/mol and passes through a minimum at about 2 molal glycerol before returning to a value of 4 kcal/mol at 4 molal glycerol. Exchange rates for lysozyme have been analyzed with transition state and Kramers's theories. The activation parameters for exchange of protons in lysozyme in the presence of 5 molal glycerol show a similar qualitative behavior to those determined for exchange in the absence of glycerol [R. B. Gregory et al. (1982) Biochemistry 24, 6523–6530]. The activation enthalpies and entropies for the fast‐exchanging protons show a gentle increase as H(t), the number of hydrogens remaining unexchanged, decreases. By contrast, the activation parameters for the slowest exchanging protons [H(t) < 20] increase dramatically as H(t) decreases. As in water, the activation parameters for exchange of the fast‐ and slow‐exchanging protons in glycerol solution are characterized by two distinct compensation temperatures (510 ± 100 K for the fast protons and 340 ± 40K for the slow protons). These values are not significantly different from those determined for exchange in water.The activation parameters, ΔH‡, and TΔS‡, are both several kcal/ mol lower for exchange in glycerol solutions compared with water. Enthalpy and entropy changes for the thermal unfolding of lysozyme in glycerol solutions [results of K. Gekko (1982) J. Biochem. 19, 1197–1204] are larger than those determined for unfolding in water. This suggests that exchange does not involve local unfolding of segments of the protein. There is evidence for a contribution from thermal unfolding for exchange of the slowest protons in glycerol solutions which is not observed in water.Analysis of exchange rates for the fast protons as a function of temperature and viscosity with Kramers' equation provides values of the viscosity exponent. This is found to increase with decreasing values of H(t). These results are not easily rationalized with Gavish's model [(1980) Phys. Rev. Lett. 44, 1160] of a “position‐dependent, internal protein viscosity” and suggest that the Gavish model of the friction coefficient is incorrect. A dissection of the effect of glycerol on exchange of the fast protons into viscosity and thermodynamic contributions is not possible with the present data. Both factors are suggested to influence exchange of the fast protons.
The irreversible binding of 2‐site ligands to hetereogeneous polymers
Authors: Schumaker Mark F. , Epstein Irving R. 
Published: December 2004

AbstractWe obtain an analytical solution for the binding of 2‐site ligands to a heterogeneous lattice. The model also describes the kinetics of chemical reactions between adjacent pendant groups of a copolymer. Our analysis is based on the principle of independence, as formulated by Gonzalez and Hemmer. Several special cases are solved in closed form; a power series solution is developed for the general problem. The results may be modified to take into account fixed total ligand. We also analyze competition between 1‐site and 2‐site ligands. As an illustration of the results, we examine in detail the kinetics and final extent of binding for two special cases.
Peptide design: Influence of a guest Aib‐Pro segment on the stereochemistry of an Oligo‐Val sequence—solution conformations and crystal structure of Boc‐(Val)2‐Aib‐Pro‐(Val)3‐OMe
Authors: Karle Isabella L. , Flippen‐Anderson Judith L. , Uma K. , Balaram Hemalatha , Balaram P. 
Published: December 2004

AbstractThe peptide Boc‐Val‐Val‐Aib‐Pro‐Val‐Val‐Val‐OMe has been synthesized to investigate the effect of introduction of a strong β‐turn promoting guest segment into an oligopeptide with a tendency to form extended structures. 1H‐nmr studies in solution using analysis of NH group solvent accessibility and nuclear Overhauser effects suggest an appreciable solvent dependence of conformations. In chloroform a 310‐helical structure is favored while in dimethylsulfoxide an Aib‐Pro β‐turn with extended arms on either side is suggested. In the crystal, the backbone forms a somewhat distorted 310‐helix despite the presence of a Pro residue in the middle. Among the four possible intrahelical hydrogen bonds three are of the 4 → 1 type and one 5 → 1. Head‐to‐tail NH ⃛OC hydrogen bonds link the helical molecules into continuous columns. The space group is P212121 with a = 11.320(2), b = 19.889(3), and c = 21.247(3) Å.
Linear dichroism characteristics of ethidium–and proflavine–supercoiled DNA complexes
Authors: Swenberg Charles E. , Carberry Susan E. , Geacintov Nicholas E. 
Published: December 2004

AbstractA flow linear dichroism technique is utilized to study the unwinding of supercoiled DNA induced by the binding of ethidium bromide (EB) and proflavine (PF) at different ratios r (drug added/DNA base). In the case of either EB or PF bound to linear calf thymus DNA, the reduced linear dichroism signals LD/A (LD: linear dichroism; A: absorbance, both measured at the same wavelength), determined at 258, and 520 or 462 nm (corresponding to contributions predominantly from the partially oriented DNA bases, intercalated EB, or PF, respectively) are nearly independent of drug concentration. In the case of supercoiled DNA, the magnitude of LD/A at 258 nm first increases to a maximum value near r = 0.04–0.05, and then decreases as r is increased further, mimicking the behavior of the sedimentation coefficients, viscosities, and gel electroporphoresis patterns measured by other workers at similar values of r. However, LD/A at 520 nm, which is due to DNA‐bound EB molecules, is constant within the range of r values of 0.02–0.06 in which the magnitude of LD/A determined at 258 nm due to the DNA bases exhibits a pronounced maximum. In contrast, in the case of PF, the magnitudes of LD/A determined at 258 or 462 nm are characterized by similar dependencies on r, both exhibiting pronounced maxima at r = 0.05; this parallel behavior is expected according to a simple interacalation model in which the DNA bases and drug molecules are stacked on top of one another, and in which both are oriented to similar extents in the flow gradient. The unexpected differences in the dependencies of (LD/A)258 and (LD/A)520 on r in the case of EB bound to supercoiled DNA, are attributed to differences in the net overall alignment of the EB molecules and DNA bases in the flow gradient. The magnitude of the LD signal at 258 nm reflects the overall degree of orientation of the supercoiled DNA molecules that, in turn, depends on their hydrodynamic shapes and sizes; the LD signals characterizing the bound EB molecules may reflect this orientation also, as well as the partial alignment of individual DNA segments containing bound EB molecules. The differences in the LD characteristics of the bound PF and EB molecules may be due to subtle differences in the mechanisms of binding, perhaps reflecting differences in the torsional dynamics and local rigidities in superhelical DNA [Wu et al. (1988) Biochemistry 27, 8128–8144] induced by these two different in tercalating agents.
Protein folding and chain collapse
Authors: Allegra Giuseppe , Ganazzoli Fabio , Bignotti Fabio , Bolognesi Martino 
Published: December 2004

AbstractIt is currently assumed that the folded structure of a globular protein is controlled in a highly deterministic way by its amino acid sequence. We show here that a very different although not necessarily contrasting viewpoint can be adopted. From statistical treatment of x‐ray results, we suggest that the folding pattern essentially follows the collapse to be expected on statistical‐mechanical grounds for an ideal chain effectively experiencing self‐attraction and comprising identical units, whose conformational properties are obtained as an average over the actual amino acid units. The local details of folding of each protein, obviously dictated byits amino acid sequence, can be regarded as statistical fluctuations.We consider 31 globular fragments belonging to 21 different water‐soluble, nonmembrane proteins. By the theory of chain collapse proposed by two of us [G. Allegra and F. Ganazzoli (1985) J. Chem. Phys. 83, 397], all the average intramolecular distances may be obtained. Accordingly, first an average plot of the mean‐square distances between kth neighboring amino acid units is constructed, starting from the observed crystallographic coordinates. Then the plot is basically reproduced with a wormlike chain model undergoing collapse as a result of intramolecular attractive forces. Agreement is especially good for short amino acid sequences (k ≲ 30), in which case the statistical sampling is more accurate, enabling us to determine the model parameters. The resulting mean‐square radius of gyration is also in good agreement with the experimental average, whereas the unperturbed characteristic ratio is roughly consistent with results from conformational calculations by W. L. Mattice [(1977) Macromolecules 10, 516], based on the rotational isomeric state approach.
Helix aggregation in peptide crystals: Occurrence of either all parallel or antiparallel packing motifs for α‐helices in polymorphs of Boc‐Aib‐Ala‐Leu‐Ala‐Leu‐Aib‐Leu‐Ala‐Leu‐Aib‐OMe
Authors: Karle Isabella L. , Flippen‐Anderson Judith L. , Uma K. , Balaram P. 
Published: December 2004

AbstractThree crystalline polymorphs of the helical decapeptide, Boc‐Aib‐Ala‐Leu‐Ala‐Leu‐Aib‐Leu‐Ala‐Leu‐Aib‐OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol‐ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with helix axes pointed in oppsite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side‐chain interactions or solvation. The α‐helix of the peptide in crystal A has seven 5 → 1 hydrogen bonds; the helix in crystal B is a mixed 310/α‐helix. The crystal parameters are as follows. Crystal A: C51H92N10O13·CH3OH, space group P21 with a = 10.498(1) Å, b = 18.189(3) Å, c = 16.475(3) Å, β = 99.28(1)°, Z = 2, R = 9.6% for 1860 data. Crystal B: C51H92N10O13·C3H7OH, space group P21 with a = 10.534(1) Å, b = 28.571(4) Å, c = 11.055(2) Å, β = 95.74(1)°, Z = 2, R = 6.5% for 3251 data. Crystal C: C51H92N10O13·C2H5OH, space group P21, with a = 10.450(1) Å, b = 28.442(5) Å, c = 11.020(2) Å, β = 95.44(1)°, Z = 2, R = 14.8% (isotropic) for 1948 data.
Conformational sampling using high‐temperature molecular dynamics
Authors: Bruccoleri Robert E. , Karplus Martin 
Published: December 2004

AbstractHigh‐temperature molecular dynamics as a method for conformational search was explored on the antigen combining site of McPC 603, a phosphorylcholine binding immunoglobulin. Simulations at temperatures of 500, 800, and 1500 K were run for 111.5, 101.7, and 76.3 ps, respectively. The effectiveness of the search was assessed using a variety of methods. For the shorter hypervariable loops, molecular dynamics explored an appreciable fraction of the conformational space as evidenced by a comparison to a simple theoretical model of the size of the conformational space. However, for the longer loops and the antigen combining site as a whole, the simulation times were too short for a complete search. The simulations at 500 and 800 K both generated conformations that minimized to energies 200 kcal/mole lower than the crystal structure. However, the 1500 K simulation produced higher energy structures, even after minimization; in addition, this highest temperature run had many cis‐trans peptide isomerizations. This suggests that 1500 K is too high a temperature for unconstrained conformational sampling. Comparison of the results of high temperature molecular dynamics with a direct conformational search method, [R. E. Bruccoleri & M. Karplus (1987) Biopolymers 26, 137–168]. showed that the two methods did not overlap much in conformational space. Simple geometric measures of the conformational space indicated that the direct method covered more space than molecular dynamics at the lower temperature, but not at 1500 K. The results suggest that high‐temperature molecular dynamics can aid in conformational searches.