bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three‐dimensional structure and active site of three hydrophobic molecule‐binding proteins with significant amino acid sequence similarity
Authors: Monaco Hugo L. , Zanotti Giuseppe 
Published: December 2004

AbstractWe review our work on bovine and human retinol‐binding protein (RBP), bovine beta lactoglobulin (BLG), and bovine odorant‐binding protein (OBP). These three proteins share a sequence similarity high enough to justify the proposal that their three‐dimensional structure ought to be quite similar, and they also share the function of similar or even identical hydrophobic ligand binding, although with a very different degree of specificity. Thus they constitute an ideal system to exhaustively explore the question of three‐dimensional structure prediction from sequence similarity and the related question of binding site prediction for similar ligands.We have used x‐ray diffraction techniques on single crystals of human and bovine RBP, bovine milk BLG, and bovine nasal mucosa OBP to investigate this problem. The results of these crystallographic studies indicate that to the level of resolution so far attained, the three‐dimensional structure of these three proteins is reasonably predicted from the sequence similarity. The fold is the same and structural differences are rather subtle.Finally, we present experimental evidence that the binding sites of RBP, BLG, and OBP are in different regions of the molecules. Thus, it appears that although sequence alignment has correctly predicted the protein fold, it has incorrectly predicted the hydrophobic ligand‐binding sites.
Helix formation in methylated copolymers of lysine and alanine
Authors: Bello Jake 
Published: December 2004

AbstractRandom copolymers of lysine and alanine, 2 : 1 and 1 : 1, were trimethylated on the lysine. amino groups to quaternary ammonium groups. Methylated and unmethylated polymers were prepared with Cl− or ClO as the counterion. CD spectra were measured for increasing concentration of peptide without added salt, and at constant peptide concentration in increasing NaCl or NaClO4. Unmethylated peptides, as the chloride, form α‐helix more readily than do the methylated peptides. The opposite occurs with ClO as counterion. The helix‐promoting effect of methylated lysine residues (ClO counterion) is diminished by the presence of alanine, as compared with effects when lysine is the only type of residue. The effect of methylation of proteins on helix formation may depend on the types of anionic groups with which the protein may be involved.
Early assembly pathways of type I collagen
Authors: Wallace Donald G. 
Published: December 2004

AbstractA method was developed for computing the free energy (ΔFi) of aggregates of type I collagen. The method was based on a treatment of Matheson and Flory describing phase equilibria of rigid rod polymers. It included a polymer–solvent interaction term that depended on near neighbor transfer energies. Extrahelical portions of the molecule were assigned local interaction energies differing from that assigned to the helix. Free energies of reaction for successive steps along assembly pathways (ΔFi–i+1) were computed. When allowance was made for specific pairing between extrahelical and helical domains, the so‐called D‐staggered (D = 670 Å) alignment of molecules was preferred, as opposed to a nonstaggered, or nematic, alignment. Based on ΔFi–i+1 alone, it appeared that 1D‐staggered oligomers arise first in assembly, followed later by addition of molecules in 4D alignment.Neither 4D dimers nor 4D‐8D trimers were predicted to be major intermediates in assembly. This result is contrary to previous hypotheses. When energies of activation were included in the analysis, the prediction was less certain, and specific circumstances were identified in which 4D dimers and 4D‐8D trimers were the earliest aggregated species in assembly.
Theoretical determination of conformational paths in citrate synthase
Authors: El‐Kettani M. A. Ech‐Cherif , Durup J. 
Published: December 2004

AbstractTwo methods are developed for the theoretical determination of a conformational path between two well‐documented forms, a closed form and the open form [Remington et al. (1982) J. Mol. Biol. 158, 111–152] of pig heart citrate synthase, a dimeric enzyme of 2 × 437 residues. The first method uses the minimization of the sum of the potential energies at a set of equidistant points, according to Elber and Karplus [(1987) Chem. Phys. Lett. 139, 375–380]. The initialization of the algorithm is modified to account for large‐angle rotations of many groups by performing the interpolations in the space of internal polar coordinates of a set of generalized Jacobi vectors earlier introduced by Durup [(1991) J. Phys. Chem. 95, 1817–1829] and by carefully testing all choices of directions of rotation for determining the initialized midpoint between the known forms. The path includes intermediate points, created by successive splittings of each interval into two equal parts, with a partial energy minimization performed after each splitting. The minimization encounters the well‐known local‐minima problem, which here is handled by low‐temperature molecular dynamics annealing. It is shown that the best ratio of potential energy decrease to rms deviation is achieved by running the dynamics at 50 K, as compared to 100 K and above. The main character of the path obtained is the occurrence of strong to‐and‐fro variations of some dihedral angles at specific stages along the path. The second method, which we name directed dynamics, uses only low‐temperature molecular dynamics simulations by starting trajectories from each of the two known forms with initial velocities directed toward the other one. The procedure is iterated by restarting trajectory pairs after the points of closest approach of the preceding pair. The two half‐paths thus built eventually meet after 70 iterations. This method provides a second path with strong similarities, as well as some differences, with respect to the path obtained by the first method.
Thermodynamic substantiation of water‐bridged collagen structure
Authors: Burjanadze Tengiz V. 
Published: December 2004

AbstractA solution of the problem of topology of a hydrogen bond net in a triple helix of collagen is suggested on the basis of an analysis of thermodynamic data on denaturation of phylogenetically different collagen [T. V. Burjanadze (1982), Vol. 21, pp. 1489–1501; T. V. Burjanadze, E. I. Tiktopulo, and P. L. Privalov (1987), Dokl. Akad, Nauk. USSR, Vol. 293, pp. 720–724] as well as on the earlier evaluation of the energy of the OH group of the 4−hydroxyproline bond [A. R. Ward and P. Mason (1973), Journal of Molecular Biology, Vol. 29, pp. 431–435]. It is shown that only the water‐bridged collagen structure [G. N. Ramachandran and R. Chandrasekharan (1968), Biopolymers, Vol. 6, pp. 1649–1661: G. N. Ramachandran, M. Bansal, and R. S. Bhatnagar (1973), Biochimica Biophysica Acta, Vol. 322, pp. 166–171: M. Bansal, C. Ramakrishnan, and G. N. Ramachandran (1975), Proceedings of the Indian Academy of Sciences, Vol. 82, pp. 152–164] can explain both the change of thermostability upon proline hydroxylation [J. Rosenbloom, M. Harsch. and S. Jimenez (1973), Archives of Biochemistry and Biophysics, Vol. 158, pp. 478–484] and its phylogenetic change [T. V. Burjanadze (1982)].
The CD of ligand‐DNA systems. 2. Poly(dA‐dT) B‐DNA
Authors: Lyng Reidar , Rodger Alison , Nordén Bengt 
Published: December 2004

AbstractA systematic theoretical study of the CD of [poly(dA‐dT)]2 and its complexes with achiral small molecules is presented. The CD spectra of [poly(dA‐dT)]2 and of poly(dA):poly(dT) are calculated for various DNA structures using the matrix method. The calculated and experimental spectra agree reasonably well for [poly(dA‐dT)]2 but less well for poly (dA):poly (dT). The calculated CD spectrum of [poly (dA‐dT)]2 fails to reproduce the wavelength region of 205–245 nm of the experimental spectrum. This discrepancy can be explained by a magnetic dipole allowed transition contributing significantly to the CD spectrum in this region. The induced CD of a transition moment of a molecule bound to [poly (dA‐dT)]2 is also calculated. As was the case for [poly(dG‐dC)]2, the induced CD of a groove bound molecule is one order of magnitude stronger than that of an intercalated molecule. The calculations also show considerable differences between pyrimidine‐purine sites and purine‐pyrimidine sites. Both signs and magnitudes of the CD induced into ligands bound in the minor groove agree with experimental observations. © 1992 John Wiley & Sons, Inc.
Flexible‐geometry conformational energy maps for the amino acid residue preceding a proline
Authors: Hurley James H. , Mason David A. , Matthews Brian W. 
Published: December 2004

AbstractPreviously calculated Conformational energy maps suggest that the α‐helical conformation for the residue preceding a proline is disfavored relative to the extended conformation by more than 7 kcal/mol. In known protein structures this conformation is observed, however, to occur for about 9% of all prolines. In addition, introduction or removal of prolines at theoretically unfavorable positions in proteins and peptides can have modest effects on stability and structure. To investigate the discrepancy between calculation and experiment, we have determined how the conformation of the proline affects the calculated energy. We have also explored the effect of bond length and bond angle relaxation on the Conformational energy map. The Conformational energy of the preceding residue is found to be unaffected by the conformation of the proline, but the effect of allowing covalent bond relaxation is dramatic. If bond lengths and angles, and dihedral angles within the pyrrolidine ring, are allowed to relax, a calculated energy difference between the α and β conformations of 1.1 kcal/mol is obtained, in reasonable agreement with experiment. The detailed shape of the calculated energy surface is also in excellent agreement with the observed Conformational distributions in known protein structures. © 1992 John Wiley & Sons, Inc.
Model building of DNA/RNA triple helix containing L‐deoxyadenosine
Authors: Tomioka Nobuo , Itai Akiko 
Published: December 2004

AbstractA three‐dimensional model of DNA/RNA triple helix that contains a poly(L‐deoxyadenosine) (L‐dA) chain is proposed based on computer‐assisted model building and energy calculations. The model building was performed by a new method that systematically searches possible conformations of nucleotide units in the helical chains. Two possible orientations of sugar‐phosphate chains, in which two homopyrimidine strands are parallel or antiparallel with each other, were considered in the systematic search. Several possible base‐pairing models, in which there are one Watson‐Crick base pair and one other base pair, were also considered. Many possible models selected by the systematic search were further refined through molecular mechanics calculation incorporating a helical boundary condition. The preferred model, which was selected on the basis of potential energy, was the one with Watson‐Crick and Hoogsteen base pairs and with its two polypyrimidine chains in the antiparallel orientation. The model can explain the experimental observation that poly (L‐dA) forms a stable triple helix with poly(uridylic acid) (U) but not with poly(deoxythymidylic acid) (dT). © 1992 John Wiley & Sons, Inc.
Viscoelastic behavior of fractionated ovine submaxillary mucins
Authors: McCullagh C. M. , Soby L. M. , Jamieson A. M. , Blackwell J. 
Published: December 2004

AbstractSolution properties of fractionated ovine submaxillary mucin (OSM) and asialo OSM (aOSM) in aqueous guanidine hydrochloride have been investigated using light scattering and Theological methods. For the first time we present viscometric evidence in both dilute and concentrated solution that the molecular structure of OSM is that of a wormlike chain. The intrinsic viscosity shows molecular weight dependence consistent with the linear extended chain conformation observed by light scattering measurements. The viscoelastic behavior of the OSM fractions in aqueous guanidine hydrochloride was further examined above the overlap concentration as a function of molecular weight and temperature. Under these solvent conditions in which the role of nonbonding intermolecular interactions is minimized, OSM shows predominantly fluid like behavior. However, high molecular weight OSM shows evidence of the existence of an entanglement network at high concentration. The frequency‐dependent shear storage and loss moduli at all concentrations and molecular weights can be scaled to yield a master curve by incorporating typical viscoelastic shift parameters. The entanglement molecular weight and concentration are consistent with literature data for extended, semiflexible wormlike chains. The behavior of aOSM is similar to that of intact OSM at comparable degrees of coil overlap, indicating that the terminal sialic acid residue on the carbohydrate side chain has no effect on the rheology of concentrated OSM solutions beyond that due to an increase in the hydrodynamic volume. © 1992 John Wiley & Sons, Inc.
Interaction of substance P and its N‐ and C‐terminal fragments with Ca2+: Implications for hormone action
Authors: Ananthanarayanan Vettai S. , Orlicky Stephen 
Published: December 2004

AbstractIn an attempt to understand the role of Ca2+ on the bioactive conformation of peptide hormones, we have examined the interaction between Ca2+ and the neuropeptide substance P. Using CD spectroscopy to monitor conformational changes caused by Ca2+ binding, we found no significant binding of the cation by substance P in water. However, a substantial conformational change occurred in the hormone on Ca2+ addition in trifluoroethanol or an 80:20 (v/v) mixture of acetonitrile and trifluoroethanol. A biphasic binding of Ca2+ was observed in these solvents with saturation at 2 cations per hormone molecule. Mg2+ caused a relatively smaller conformational change in the hormone. A peptide corresponding to residues 1–7 at the N‐terminal fragment of substance P showed a weak nonsaturating binding of Ca2+ in the nonpolar solvents whereas the 7–11 C‐terminal fragment peptide displayed a binding indicative of an 1 : 1 Ca2+ / peptide complex. Ca2+ binding by the hormone and the 7–11 fragment was also monitored by changes in fluorescence of the phenylalanyl residues. The results support the conclusion drawn from the CD data about a distinct Ca2+ binding site in the C‐terminal part of substance P. The Kd values obtained from fluorescence data were 160 µM for Ca2+ and 1 mM for Mg2+ binding by substance P. The hormone and the two peptide fragments were also tested for their effect on the stability of dimyristoyl lecithin vesicles. Substance P and the N‐terminal fragment caused no significant leakage of either fluorescent dyes or K+ trapped in the vesicles. Nor did they cause membrane fusion as monitored by the fluorescence quenching method. In contrast, the C‐terminal 7–11 fragment caused considerable leakage of vesicular contents and promoted membrane fusion. When tested for their ability to translocate Ca2+ across the lipid bilayer in dimyristoyl lecithin vesicles containing the Ca2+ indicator Arsenazo III, both substance P and the 7–11 fragment showed significant Ca2+ transport while the 1–7 fragment showed negligible transport. The apparent transport of the 7–11 fragment is attributable to its effect on the integrity of the bilayer membrane. These data distinguish the N‐ and C‐terminal domains of substance P in terms of their lipid‐dependent interaction with Ca2+. In light of the requirement of extracellular Ca2+ for substance P action, the data are also suggestive of the possibility of the involvement of Ca2+ in the bioactive conformation of this hormone and in its interaction with the receptor. © 1992 John Wiley & Sons, Inc.
Characterization of β‐turns in cyclic hexapeptides in solution by fourier transform IR spectroscopy
Authors: Mantsch H. H. , Perczel A. , Hollósi M. , Fasman G. D. 
Published: December 2004

AbstractThe β‐turn represents a structural element frequently encountered in globular proteins. However, in spite of various theoretical and experimental studies the ir signature bands of pure β‐turns are still not established beyond doubt. Although considerable information exists now on the ir spectra of β‐helical and β‐sheet structures, the lack of knowledge concerning turn structures in general, and that of β‐turns in particular, presents a major uncertainty in the estimation of global protein secondary structures from ir spectroscopic data. To obtain more specific information about the characteristic amide bands in β‐turns, we report herein an ir spectroscopic analysis of a series of five cyclic pseudo‐hexapeptides known to form β‐turns from previous CD and nmr studies [A. Perczel, M. Hollósi, B. M. Foxman, and G. D. Fasman (1991) Journal of the American Chemical Society, Volume 113, pp. 9772‐9784 ]. We show here that in these cyclic peptides the amide groups involved in β‐turns that comprise a ten‐membered hydrogen‐bonded ring (and represent the first H‐bond pair in a β‐sheet), give rise to characteristic amide I bands in the range 1638–1646 cm−1, with the exact position depending on the solvent and the nature of the side‐chain substituents. © 1993 John Wiley & Sons, Inc.
Approximation and characterization of molecular surfaces
Authors: Duncan Bruce S. , Olson Arthur J. 
Published: December 2004

AbstractThe representation and characterization of molecular surfaces are important in many areas of molecular modeling. Parametric representations of protein molecular surfaces are a compact way to describe a surface, and are useful for the evaluation of surface properties such as the normal vector, principal curvatures, and principal curvature directions. Simplified representations of molecular surfaces are useful for efficient rendering and for the display of large‐scale surface features. Several techniques for representing surfaces by expansions of spherical harmonic functions have been reported, but these techniques require that the radius function is single valued, that is, each ray from an origin inside the surface intersects the surface at one and only one point. A new technique is described that removes this limitation and can be used to compute surface shape properties. © 1993 John Wiley & Sons, Inc.
Dynamic light scattering of aqueous solutions of linear aggregates induced by thermal denaturation of ovalbumin
Authors: Nemoto Norio , Koike Akihiro , Osaki Kunihiro , Koseki Taihei , Doi Etsushiro 
Published: December 2004

AbstractDynamic light scattering measurements were performed on dilute aqueous solutions of native ovalbumin (OA) and on those of linear OA aggregates induced by thermal denaturation at low ionic strength and neutral pH. The weight‐average molecular weight Mw of four aggregates tested ranged from 1,700,000 to 5,500,000. The translational diffusion coefficient D0 of native OA at infinite dilution was estimated as 8.70 × 10 −7 cm2/s, which gave 56.0 Å as the diameter of the rigid spherical particle. The intensity autocorrelation function of linear OA polymers was analyzed with the cumulant method to obtain the first cumulant Λe. The dependence of Λe on the scattering vector q at very low polymer concentration was found intermediate between those of a flexible chain and a rigid rod. The translational diffusion coefficient Dtr [≡ (Te/q2)q → 0] was in proportion to M, and the magnitude was in good agreement with a value calculated from the wormlike cylinder model with values of three parameters determined in an earlier study, ML = 1600 Å−1, d = 120 Å, and Q = 230 Å, where ML, d, and Q are the molecular weight per unit length, diameter, and persistence length, respectively. Based on these results, a new model, to be called as the dimer model, was proposed to interpret the formation mechanism of linear OA polymers induced by thermal denaturation. © 1993 John Wiley & Sons, Inc.
Design of peptides: Crystal and molecular structure of a 310‐helical peptide N‐Boc‐L‐Phe‐dehydro‐Phe‐L‐Val‐L‐Phe‐dehydro‐Phe‐L‐Val‐Och3
Authors: Padmanabhan B. , Singh T. P. 
Published: December 2004

AbstractHighly specific peptide structures can be designed by inserting dehydro residues into peptide sequences. The peptide N‐Boc‐L‐Phe‐dehydro‐Phe‐L‐Val‐L‐Phe‐dehydro‐Phe‐L‐Val‐OCH3, synthesized by conventional procedures, crystallizes from methanol‐‐water mixtures at 4°C in the tetragonal space group P43 with cell parameters a = b = 13.829 ± 0.003 Å, c = 27.587 ± 0.008 Å, V = 5275.5 ± 0.2 Å3, Z = 4, dm = 1.152 ± 0.005 g cm−3, dcal = 1.150 ± 0.005 g cm−3. The overall residual factor R = 0.084 for 2342 reflections, with 2θmax = 140° using CuKα radiation. The backbone torsion angles are θ1 = −171(1)°, ω0 = 168 (1)°, ϕ1 = 77 (2)°, ψ1 = 41 (2)°, ωl = 169 (1)°, ϕ2 = −46 (2)°, ψ2 = ‐24 (2)°, ω2 = 179 (1)°, ϕ3 = −63 (2)°, ϕ3 = −19 (2)°, ω3 = 171 (1)°, ϕ4 = −67 (2)°, ψ4 = −8 (1)°, ω4 = 169 (1)°, ψ5 = −61 (1)°, ϕ5 = −26(1)°, ω5 = 177(1)°, ψ6 = −122 (1)°, ϕ = 26 (2)°. The peptide adopts a 310‐helical conformation with three intramolecular hydrogen bonds (i + 3 → i) involving carbonyl oxygen atoms of Phe1, dehydro‐Phe2, Val3, and the NH groups of Phe4, dehydro‐Phe5, and Val6 with distances of 3.01 (1), 2.82 (1), and 3.09 (2) Å, respectively. The structure determination revealed that a hexapeptide with two dehydro‐Phe residues at (i + 2) and (i + 5) positions generates a 310‐helical conformation. The helical peptide molecules are arranged in a major helical arrangement about the 43axis. These helices are packed parallel to the c axis and form several interdigitating hydrogen bonds. The interhelix hydrogen‐bonding regions are separated by van der Waals interactions involving the side chains of Phe, dehydro‐Phe, and Val residues. © 1993 John Wiley & Sons, Inc.
Synthesis, biological activity, and conformational analysis of [pGlu6, N‐MePhe8, Aib9] substance P (6–11): A selective agonist for the NK‐3 receptor
Authors: Tallon M. , Ron D. , Halle D. , Amodeo P. , Saviano G. , Temussi P. A. , Selinger Z. , Naider F. , Chorev M. 
Published: December 2004

AbstractA highly potent and selective agonist to the tachykinin NK‐3 receptor, [pGlu6, N‐MePhe8, Aib9] substance P (6–11) (I), was synthesized via the solid phase method. The ED50 of I was 4n M in the guinea pig ileum in the absence of atropine (NK‐1 + NK‐3 receptors) and this agonist was 5000‐fold less potent in the presence of atropine (NK‐1 receptor). The analogue was virtually inactive in the rat vas deferens (NK‐2 receptor). A detailed analysis of the solution conformation of this analogue in DMSO‐d6 and in a DMSO‐d6 H2O cryornixture was carried out by a combination of 1H‐nmr 2D techniques (DQF‐COSY, TOCSY, NOESY and ROESY) and model building based on empirical energy calculations. Peptide I exists as a mixture of isomers containing cis and trans Phe‐N‐MePhe peptide bonds. The main isomer, containing a cis Phe‐N‐MePhe peptide bond, shows a preferred folded conformation characterized by a type VI β‐turn with Phe and N‐MePhe in the i + 1 and i + 2 positions. The turn is followed by a helical segment extending to the C‐terminal. This conformation is compared to previously reported conformations of other selective tachykinin agonists and may be a promising lead for the design of novel NK‐3 agonists with additional conformational constraints. © 1993 John Wiley & Sons, Inc.