摘要:

AbstractA complete analysis of all possible conformations with correct hydrogen bonds of the collagen II type was performed on the basis of developed simultaneous equations. Using a unimodal search (by varying Ψ3), the energetically favorable structure was obtained. No other energetically satisfactory structural solutions are possible. The next aim was to obtain a precise model of the molecule. The program used includes a subroutine for continual deformation of the pyrrolidine rings. The set of parameters determining the structure consists of 14 independent variables (8 dihedral and 6 bond angles). As starting points for the energy optimization, conformations produced by scanning and some structures from previous work were used. The final structures (practically the same for both polymers) have helix parametersh= 0.285 nm andt= 52°, which are in excellent agreement with the 7/2 symmetry of diffraction data. The conformations of the pyrrolidine rings are of the B type, i.e., C2‐Cβ‐exo‐Cγ‐endo. For both polypeptides, the conformations of imino acids in position 3 of the triplet are the same; in position 2, however, they are slightly different. The difference in diffraction patterns for the 7/2 and 10/3 helices i

ISSN:0006-3525    

DOI:10.1002/bip.360210302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractTheB‐to‐Aconformational transition of calf thymus DNA fibers was followed employing Raman spectroscopy. The transition was induced by soaking DNA fibers in water/ethanol mixtures increasing from 60 to 85% ethanol (v/v). Intensity changes of 17 Raman vibrational bands were quantified in the region from 400 to 860 cm−1. Two bands at 500 and 784 cm−1were employed as internal standards. These bands do not appear to change in intensity with ethanol concentration. Large intensity changes relative to these two bands are observed between 70 and 74% ethanol for backbone vibrations at 708, 808, and 835 cm−1, and base vibrations at 682, 730, and 750 cm−1. These results indicate that a highly cooperative conformational change takes place between different portions of DNA in theB‐to‐Atransition. Relative intensity changes preceding the onset of the major transition are observed in only two bands; at 835 cm−1, assigned to a ribose–phosphate vibration, and at 750 cm−1, assigned to thymine. The implications of these pretransition

ISSN:0006-3525    

DOI:10.1002/bip.360210303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe x‐ray structure of the hydrated ammonium salt of the deoxytetranucleotide d‐pApTpApT was determined by Patterson and direct methods at a resolution of 1 Å. The crystal structure contains right‐handed double‐helical segments formed by complementary Watson‐Crick‐type hydrogen bonding between the adenine and thymine bases of neighboring molecules. The minihelix contains two base pairs. The chains are antiparallel. The A‐T and T‐A sequences have different phosphodiester conformations. The deoxyribose‐pucker and the sugar–base orientation alternate along the chain depending on the nature of the base (3′‐endofor purine and 2′‐endofor pyrimidine). The extended structure is stabilized by base–base, base–sugar, and hydrogen‐bond interactions. The minihelix of two base pairs provides starting coordinates for model‐building studies of the dA‐dT polymer. A B‐DNA‐type polymer structure is described, which has sequence‐dependent alternations of both the deoxyribose pucker and the phosphate diester bridge conformation. Such sequence‐dependent DNA structures, if present locally in regions such as operator sequences, could facilitate sequence‐specific interactions. The crystal study also suggests possible

ISSN:0006-3525    

DOI:10.1002/bip.360210304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractAnalysis of the amino acid sequence of glycoproteins has suggested the β‐turn as a likely site of glycosylation in glycoproteins. According to this model, the peptide chain traverses the interior of a globular protein, reversing its direction at the protein surface, a likely point for the attachment of hydrophilic carbohydrate residues. In order to search for plausible conformations of glycosylated β‐turns in asparagine‐linked glycoproteins, we have adapted the conformational energy calculation method of Scheraga and coworkers for use in carbohydrates. The parameters for nonbonded and hydrogen‐bonded interactions have been published, and electrostatic parameters are derived from a CNDO calculation on a model glycopeptide. Our results indicate that the orientation of the glycosyl amide bond having the amide proton nearlytransto the anomeric proton of the sugar has the lowest energy. Although CD and nmr experiments in our laboratory have consistently found this conformation, our calculations show the conformation having these two protons in acisrelationship to lie very close in energy. Calculations on the glycopeptide linkage model, α‐N‐acetyl, δ‐N(2‐acetamido‐1,2‐dideoxy‐β‐D‐glucopyranosyl)‐N′‐methyl‐L‐asparaginyl amide show that several distinct geometries are allowed for glycosylated β‐turns. For a type I β‐turn, three conformations of the glycosylated side chain are found within 4 kcal of the minimum, while two conformations of the glycosylated side chain are allowed for a type II turn. The hydrogen‐bonded C7 conformation is also allowed. Stereoviews of the low‐energy conformations reveal no major hydrogen

ISSN:0006-3525    

DOI:10.1002/bip.360210305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe CD spectrum of the enzyme adenylate kinase has been investigated. Theoretical calculations, based on the x‐ray crystal structure, have been carried out by means of an origin independent matrix formalism. The entire molecule was included in the calculations in the sense that essentially all electronic transitions that occur at wavelengths longer than 185 nm were included in the basis set. A linear dielectric function was utilized to evaluate the intertransition coupling potentials. The results of the theoretical calculations were in reasonable agreement with experimental CD spectra of the molecul

ISSN:0006-3525    

DOI:10.1002/bip.360210306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractA method of calculating time correlation functions from records of computer simulated equilibrium conformational fluctuations in a globular protein is discussed. Use of the calculated time correlation function for discussions of dynamics of folding and unfolding transition in the two‐dimensional lattice model of proteins. The time correlation functions can be approximated in general by a sum of two simple exponential terms. The relaxation time of the slower mode does not depend on the nature of the physical quantity with respect to which the time correlation function is calculated. This time characterizes the overall folding and unfolding transition. The relaxation time of the faster mode depends on the nature of the physical quantity and characterizes conformational fluctuations within each of the native and denatured states. The mechanism of a previously observed phenomenon of the acceleration of the folding and unfolding transition by short‐range interactions is discus

ISSN:0006-3525    

DOI:10.1002/bip.360210307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractAnalysis of the mutual diffusion coefficient of hyaluronate reveals that it rapidly increases with increasing concentration or decreasing ionic strength. The mutual diffusion coefficients analyzed by boundary relaxation in the analytical ultracentrifuge by either Raleigh interference optics or absorption optics (through the use of fluorescein‐labeled hyaluronate) yielded similar values. The theoretical treatment of the mutual diffusion coefficient has been analyzed in terms of experimentally measured intradiffusion coefficients and thermodynamic virial coefficients. Only approximate agreement between theory and experiment was found. The concept of formation of transient statistical network structures in semidilute solutions of hyaluronate was applied to evaluate a critical concentration at which network formation occurs. This has been discussed in relation to the marked decrease in the intradiffusion coefficient of hyaluronate with concentration. The formation of network structures in hyaluronate was found not to preclude the hyaluronate undergoing extremely rapid rates of mutual diffusion (with diffusion coefficients ∼30 × 10−11m2s1) under conditions of relatively large initial chemical potential gradients. Measurements of the unidirectional flux of hyaluronate for nonzero gradients demonstrated their marked sensitivity to the magnitude of the concentration difference across the boundary. An experimental feature of the unidrectional diffusion coefficients of hyaluronate is that they may be analyzed purely in terms of mutual and intradiffusion processes. The backflux diffusion coefficient (describing the flux against the imposed concentration gradient) appeared identical with the intradiffusion coefficient. The analysis of the various sources of errors made in this study suggests that the magnitude of the diffusion coefficients measured may be regarded only as appro

ISSN:0006-3525    

DOI:10.1002/bip.360210308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractA major component of pigment gallstones (PS) is a black, insoluble substance. It has been suggested that this pigment material might be a highly crosslinked polymer, and if such were the case, it should imbibe solvent (swell) to the maximum permitted by the crosslinks of its macromolecular network. We measured the equilibrium amount,qeq, by which pulverized, desiccated PS swells in different liquids, including isotonic aqueous buffers at pH values from 1.5–11.5. For ionic strengths ≥ 0.15, the dependence ofqeqon pH exhibits a broad titration curve with a midpoint near pH 7.qeqwas<1.2 in methanol, dimethylformamide, dimethylsulfoxide, and chloroform. The ir absorbance from vinyl groups in the black pigment was only one‐eighth that of unconjugated bilirubin, the primary chemical building block of PS; this implicates vinyl groups in the formation of a polymer network. The rise inqeqwith increasing pH suggests that the carboxyl groups are free to ionize and are therefore not involved in the covalent bonds that make the crosslinked polymer. A network polymer structure would account for the inability to dissolve PS in those solvents in which unconjugated bilirubin is so

ISSN:0006-3525    

DOI:10.1002/bip.360210309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractA distance constraint approach is applied to two‐dimensional models of proteins in order to visualize the nature of protein folding and to examine the relative roles of different ranges of interaction. Three different native structures (I, II, and III) are considered; they have two different kinds of residues, viz., hydrophobic and hydrophilic, and different sequences of these residues. We examine how the distance constraint approach functions in the prediction of protein folding when we know the sequence of the residues, the (fixed) bond lengths, the mean distances between residuesiandi+ 2, andiandi+ 3, and the mean distances for hydrophobic–hydrophobic, hydrophobic–hydrophilic, and hydrophilic–hydrophilic contacts between residuesiandi+j, wherej≥ 4. This approach involves optimization of an object function with respect to 98 variables and is not free of the multiple‐minimum problem. The optimization is always terminated if the chain is entangled and/or the segments (residues) are packed too compactly to move. In order to escape from such situations and to take the excluded‐volume effect into account, a Monte Carlo method is used after the optimization is trapped in local minima. Success in the prediction of folding is found to depend on the starting conformations and on the native conformations. Fair success is obtained in predicting the helix‐like structure in protein I and the overall structure of protein III, but not the β‐like structures of proteins I and II. Insofar as the prediction of the structure of protein III is reasonable, it appears that some sequences of residues produce greater constraints on their conformations than others, if one considers only the hydrophobic and hydrophilic nature of the residues. These results imply that, in the folding of real proteins in three dimensions, the competition for hydrophobic (and hydrophilic) residues for inside (outside) positions in the molecule probably constitutes a necessary but not a sufficient condition to form and stabilize the native structure. The failure to predict the structure of protein II, and part of that of protein I, suggests that there are two types of long‐range interactions. One (which we considered here) is nonspecific (i.e., is defined only in terms of contacts between residues of the same or different polarity) and acts at any stage of protein folding; the other (which we did not consider here) is a specific interaction between residues in pairs and contributes only when the residues in the specific pair take on the native conformation. Presumably, incorporation of such specific long‐range interactions, together with the nonspecific ones, is necessary for successful protein folding, using the distan

ISSN:0006-3525    

DOI:10.1002/bip.360210310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY

摘要:

AbstractThe mode of action of many antitumor agents entails the inhibition of nucleic acid synthesis. Because many of the drugs can intercalate, it is assumed that intercalation is an important step in the mechanism of biological activity. As intercalants contain a planar chromophore as an ingredient essential for intercalation, chromophores that should fit into DNA are desired. This is the main theme of this investigation. Binding to DNA of fundamental moieties, protonated pyridine, aniline, phenol, quinone, and 4H‐thiopyran‐4‐one, is studied to determine their optimum placement in DNA. The optimum orientations for each moiety are superimposed to form polyaromatic systems that can intercalate in a manner in which functional groups on these chromophores are oriented as in the moieties themselves. Ideal intercalants proposed contain three and four fused ring system, have protonated ring nitrogen atoms located to maximize the electrostatic interactions with DNA, hydroxy and amino groups that can hydrogen bond to the OIIand O5′phosphate backbone atoms, and carbonyl and sulfur groups in the central position of the ring system to provide variations in the chromophore and to interact with the relatively positive region in the intercalation site. The optimum orientation occurs when the chromophore and the base pairs overlap to the maximum extent. The ideal intercalants are fundamentally of t

ISSN:0006-3525    

DOI:10.1002/bip.360210311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1982

数据来源: WILEY