摘要:

AbstractA combination of detailed energy minimization and molecular dynamics studies of closed circular DNA offers here new information that may be relevant to the dynamics of short DNA chains and/or low superhelical densities. We find a complex dependence of supercoiled DNA energies and geometries on the linking number difference ΔLkas physiological superhelieal densities (|σ| ∼ 0.06) are approached. The energy minimization results confirm and extend predictions of classical elasticity theory for the equilibria of elastic rods. The molecular dynamics results suggest how these findings may affect the dynamics of super‐coiled DNA.The minimization reveals sudden higher order configurational transitions in addition to the well‐known catastrophic buckling from the circle to the figure‐8. The competition among the bending, twisting, and self‐contact forces leads to differentfamiliesof supercoiled forms. Some of those families begin with configurations of near‐zero twist. This offers the intriguing possibility that nicked DNA may relax to low‐twist forms other than the circle, as generally assumed. Furthermore, for certain values of ΔL

ISSN:0006-3525    

DOI:10.1002/bip.360340502

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe DNA interaction of derivatives of ellipticine with heterocyclic ring systems with three, four, or five rings and a dimethylaminoethyl side chain was studied. Optical spectroscopy of drug complexes with calf thymus DNA, poly [(dA‐dT) · (dA‐dT)], or poly [(dG‐dC) · (dG‐dC)]showed a 10 nm bathochromic shift of the light absorption bands of the pentacyclic and tetracyclic compounds upon binding to the nucleic acids, which indicates binding by intercalation. For the tricyclic compound a smaller shift of 1–3 nm was observed upon binding to the nucleic acids.Flow linear dichroism studies show that the geometry of all complexes is consistent with intercalation of the ring system, except for the DNA and poly [(dG‐dC) · (dG‐dC)] complexes of the tricyclic compound, where the average angle between the drug molecular plane and the DNA helix axis was found to be 65°.One‐dimensional1H‐nmr spectroscopy was used to study complexes between d(CGCGATCGCG)2and the tricyclic and pentacyclic compounds. The results on the pentacyclic compound show nonselective broadening due to intermediate chemical exchange of most oligonucleotide resonances upon drug binding. The imino proton resonances are in slow chemical exchange, and new resonances with upfield shifts approaching 1 ppm appear upon drug binding, which supports intercalative binding of the pentacyclic compound. The results on the tricyclic compound show more rapid binding kinetics and very selective broadening of resonances. The data suggest that the tricyclic compound is in an equilibrium between intercalation and minor groove binding, with a preference to bind close to the AT base pairs with the side chain residing in the minor groove. © 199

ISSN:0006-3525    

DOI:10.1002/bip.360340503

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe linear nonapeptide hormone bradykinin (Arg1‐Pro2‐Pro3‐Gly4‐Phe5‐Ser6‐Pro7‐Phe8‐Arg9) is involved, either directly or indirectly, in a wide variety of physiological processes, particularly pain and hyperanalgesia. Additional evidence suggests that bradykinin also plays a major role in inflammatory response, asthma, sepsis, and symptoms associated with the rhinoviral infection. It has long been speculated that a β‐turn at the C‐terminus of bradykinin plays a major role in the biological activity of the neuropeptide. The β‐turn forming potential of bradykinin in three vastly different local chemical environments, DMSO, 9 : 1 dioxane/water, and in the presence of 7.4 mMlyso phosphatidylcholine micelles, was investigated using two‐dimensional homonuclear nmr experiments coupled with simulated annealing calculations. The results of these investigations show that in all three systems residues 6–9 of the C‐terminus adopt very similar β‐turn like structures. These results suggest that the β‐turn at the C‐terminus of bradykinin is an important secondary structural feature for receptor recognition and

ISSN:0006-3525    

DOI:10.1002/bip.360340504

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

年代:1994

数据来源: WILEY

摘要:

AbstractIsoenergy surfaces were calculated for the α‐ and β‐anomers of isomaltose and gentiobiose, based on 46,656 conformers for each disaccharide. Low‐energy regions exist for each of the three staggered positions about the C‐5′  C‐6′ bonds, and known crystal structures lie in two of these regions. As expected, the molecular partition function showed greater flexibility for these three‐bond‐linked disaccharides than for comparable two‐bond‐linked structures. A model miniature crystal of gentiobiose accounts for most of the remaining structural differences between the modeled isolated molecule and the crystal structure. Based on models of isolated molecules of isomaltose and gentiobiose, the predicted Boltzmann‐weighted nmr coupling constants were satisfactory, as were predicted optical rotations for gentiobiose.

ISSN:0006-3525    

DOI:10.1002/bip.360340505

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

年代:1994

数据来源: WILEY

摘要:

AbstractUsing dynamic light scattering (DLS), we have measured the diffusion coefficient and internal motions of narrow topoisomer distributions of pUCl8 DNA (2687 base pairs) as a function of linking number. The topoisomer distributions were prepared by C‐18 reversed phase high performance liquid chromatography separation of topoisomerase I/ethidium‐generated topoisomer families. The measured diffusion coefficients agree well with those predicted by a Monte Carlo model for the generation of equilibrium ensembles of DNA topoisomers of defined linking number. The only parameters used in the model were the bending persistence length, torsional rigidity, and hydrodynamic radius of DNA known independently from other techniques. Two different values for the torsional rigidity, α = 4 · 10−12and 8.8 · 10−12dyn cm, were used. Intrachain interactions in the DNA were taken into account by using an “effective DNA radius,” which was varied betweenrDNA= 1–8 nm. The best agreement between the measured and calculated values was obtained for α = 4 · 10−12dyn cm,rDNA= 4 nm. The internal motions of the DNA topoisomers were characterized by the amplitude of the fast relaxation of the DLS autocorrelation function. Our earlier result that supercoiling leads to a decrease in the amplitude of internal motion was confirmed. In addition, we see a characteristic maximum of the internal motion amplitude at a superhelix density of σ = −0.03. The maximum occurs in the same range as a structural transition in pUC8 dimers previously described by L. Song et al. (1990 J. Mol. Biol.214, 307–326). ©

ISSN:0006-3525    

DOI:10.1002/bip.360340506

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe solution structure of a peptide fragment corresponding to the 38–59 region of porcine phospholipase A2has been investigated using CD, nmr chemical shifts, and nuclear over‐hauser effects (NOEs). This isolated fragment of phospholipase forms an α‐helix spanning residues 38–55, very similar to the one found in the native protein, except for residues 56–58, which were helical in the crystal but found random in solution. Addition of triflouro‐ethanol (TFE) merely increased helix population but it did not redefine helix limits. To investigate how the folding information, in particular that concerning eventual helix start and stop signals, was coded in this particular amino acid sequence, the helices formed by synthetic peptides reproducing sections of this phospholipase 38–59 fragment, namely 40–59, 42–59, 38–50, and 45–57, were characterized using NOEs and helix populations quantitatively evaluated on different peptide chain segments using nmr chemical shifts in two solvents (H2O and 30% TFE/H2O). A set of nmr spectra was also recorded and assigned under denaturing conditions (6Murea) to obtain reliable values for the chemical shifts of each peptide in the random state. Based on chemical shift data, it was concluded that the helix formed by the phospholipase 38–59 fragment was not abruptly, but progressively, destabilized all along its length by successive elimination of residues at the N end, while the removal of residues at the C end affected helix stability more locally and to a lesser extent. These results are consistent with the idea that there are not single residues responsible for helix initiation or helix stability, and they also evidence an asymmetry for contributions to helix stability by residues located at the two chain ends. The restriction of molecular mobility caused by linking with a disulphide bridge at Cys 51 two identical 38–59 peptide chains did not increase helix stability. The helix formed by the covalently formed homodimer was very similar in length and population to that formed by the monomer.

ISSN:0006-3525    

DOI:10.1002/bip.360340507

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

年代:1994

数据来源: WILEY

摘要:

AbstractA 16‐residue amphiphilic oligopeptide (EAK16) with every other residue alanine and also containing glutamic acid and lysine (Ac‐NH‐AEAEAKAKAEAEAKAK‐CONH2) is able to form an unusually stable β‐sheet structure. The β‐sheet structure is stable at very low concentrations in water and at high temperatures. Various pH changes at 1.5, 3, 7, and 11 had little effect on the stability of the β‐sheet structure. The β‐sheet structure was not altered significantly even in the presence of 0.1% SDS, 7 molar guanidine hydrochloride, or 8 molar urea. One of the structural characteristics of the EAK16 is its ionic self‐complementarity in that ionic bonds and hydrogen bonds between Glu and Lys can form readily between two oligopeptide β‐sheet structures. This structural feature is probably one of the factors that promotes its extreme stability. This is the first example of such an extended ionic self‐complementarity in a protein structure. EAK16 and its related peptides may have applications as useful biomaterials. It also offers a good model for studying the mechanism of β‐sheet formation. Because the oligopeptide can self‐assemble to form a membranous structure, it may have relevance to origin of life resear

ISSN:0006-3525    

DOI:10.1002/bip.360340508

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

年代:1994

数据来源: WILEY

摘要:

AbstractAn Ising network consists of a set ofNunits existing in two possible states, 0 and 1. If two units contact each other in the network, there is a nearest neighbor interaction that depends only on the states of the units. If an Ising network can be split into two independent subsystems by deleting the contact between two units, then these units specify each other's site‐specific properties and the state of either unit uniquely specifies the state of the other. This theorem holds regardless of (a) the dimensional embedding of the network as a whole, (b) the precise interaction geometry among the units within either subsystem, and (c) the intrinsic energy for the 0 → 1 switching of any given unit. Either subsystem in the network can be considered as a probe for the state of the unit in the other subsystem to which the probe is connected. Application of the theorem to the analysis of the site‐specific properties of the biologically relevant case of a linear network, or heteropolymer, yields a rather counterintuitive result. Knowledge of the state of the end unit in the network, as a function of the change in the thermodynamic driving force for the 0 → 1 transition, is sufficient to completely resolve the energetics of the network. © 1994 John Wiley&S

ISSN:0006-3525    

DOI:10.1002/bip.360340509

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe receptor for the α‐factor mating pheromone of the yeastSaccharomyces cerevisiaeconsists of 431 amino acid residues and is a member of a family of membrane proteins predicted to have seven transmembrane helices. Fragments of the receptor corresponding to two of the transmembrane helices [residues 246–269 (M6) and 273–302 (M7)], two of the interhelical loops [residues 107–125 (E2) and 191–206 (E3)], and to a portion of the carboxyl terminus [residues 350–372 (CT)] were synthesized using solid‐phase methodologies and purified to near homogeneity. CD was used to characterize the secondary structure of these peptides in trifluoroethanol (TFE), in TFE/water mixtures, in sodium dodecyl sulfate (SDS), and in the presence of dimyristoyl phosphatidylcholine (DMPC) liposomes. In TFE, M6 and M7 exhibited CD spectra consistent with highly helical peptides, whereas CT was partially helical. In contrast, E2 and E3 were either disordered or aggregated in this solvent. M6 did not partition well into DMPC vesicles whereas M7 remained helical. Both M6 and M7 assumed helical conformations in 25 mMSDS. The loop neptides and the carboxyl terminus peptide were either in a β‐structure or disordered in the presence of lipid. These findings represent the first biophysical evidence for conformations assumed by specific segments of theSTE2receptor protein. © 1994 Jo

ISSN:0006-3525    

DOI:10.1002/bip.360340510

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

年代:1994

数据来源: WILEY

ISSN:0006-3525    

DOI:10.1002/bip.360340501

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

年代:1994

数据来源: WILEY