摘要:

AbstractConformational‐energy calculations were carried out on the new family of β‐lactam antibiotics (viz., thienamycin, PS‐5, 1‐oxa‐ and 1‐thiapenems, and their close analogs); these exhibit broad‐spectrum antibacterial activity and stability towards β‐lactamase‐producing strains. The bicyclic ring system in all the compounds studied was found to be highly rigid and to favor only one conformation. This is in contrast to findings in penicillins, where the five‐membered ring assumes two puckered conformations. The relative orientations of the bicyclic ring system and the nature and configuration of the substituent at C‐5 position, besides nonplanarity of the lactam peptide bond, are shown to be important for biological activity. The present study, in agreement with x‐ray studies, predicts that the lactam peptide bond in 1‐carbapenem is more nonplanar than in 1‐thiapenem. These studies also suggest that the conformational requirement of bicyclic ring system to bind to crosslinking enzyme(s) and

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200502

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

年代:1981

数据来源: WILEY

摘要:

AbstractA study of the temperature dependence of the initial transient velocities of the oxidative deamination of L‐glutamate by glutamate dehydrogenase and NADP has permitted the determination of the enthalpies, entropies, and heat capacities of the phenomenological parameters for mechanistic steps up to and including the catalytic hydrogen‐transfer step. The most striking feature observed is the extremely large negative heat capacity of activation (−590 ± 150 cal K−1mol−1) for the catalytic step itself. Possible sources of such heat capacities are considered, with particular focus on the effects of hidden equilibria among multiple thermodynamic states. Heat‐capacity changes of the sort observed here can be produced by shifts of such dynamic equilibria between multiple forms of the free enzyme induced by the formation of the catalytic tran

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200503

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

年代:1981

数据来源: WILEY

摘要:

AbstractComplex formation of valinomycin with Ba2+ions was investigated by circular dichroism spectroscopy. The results indicated that Ba2+forms entirely different types of complexes when compared with K+. The data with perchlorate salt showed evidence for the formation of less stable V2C (peptide sandwich), VC (1:1), and VC2(ion sandwich) complexes followed by a stable final complex upon gradual addition of salt (V stands for valinomycin and C for the cation). This final complex possibly has a flat structure with no internal hydrogen bonds, similar to that of valinomycin in highly polar solvents. The possible complexation mechanism and the role played by anions and isopropyl side chains are highlighted.

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200504

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe biologically active ACTH(1–32) and ACTH(1–24) and other shorter peptide segments of the native hormone ACTH(1–39) were studied in aqueous solution by13C‐nmr. In order to identify the13C resonances—except those of the carbonyls—both high‐field nmr spectroscopy measurements and substitution of residues with amino acids enriched to 85% in13C were carried out. The main results are (1) the direct characterization of thecis–transisomerism of proline 24 and its effects on the directly connected and sequentially neighboring residues and (2) findings that the conformational features agree with an α‐helix type organization in the N‐terminal part of the ACTH molecule which is responsible for the

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200505

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe binding of Mn2+to double‐stranded DNA in solution has been studied by measuring the proton‐relaxation enhancement of solvent water. The nmr experiments were carried out on DNAs of different base composition and showed the existence of weak and tight binding sites for Mn2+. The former sites are related to the electrostatic binding of the divalent cation with two contiguous phosphate groups, and the latter appear to vary almost proportionally with the number of G·C base pairs in the DNAs. Our results agree, in general, with the emerging evidence for a specific interaction of Mn2+with the G·C residues of DNA. Competition experiments with Mg2+suggested that this binding of Mn2+in DNA also involves the phosphate groups. More definitely, our data conform with the hypothesis made by Clement et al. of Mn2+chelation between the phosphate and the nitrogen N7 of a deoxyguanyl unit o

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200506

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe specificity of the interaction between the α‐helices in two‐chain coiled‐coils is investigated by studying the formation of hybrid molecules in which one α‐helix is a clam paramyosin chain and the other a worm paramyosin chain. Hybrids are formed by mixing, denaturation, and subsequent renaturation. Comparison is made with a blank solution in which renaturation precedes mixing, thus precluding hybridization. Hybrids are detected by a ruse based on the presence of free sulfhydryl functions on calm chains. This allows molecules comprising two clam chains to be covalently crosslinked by oxidation with 5,5′‐dithiobis(2‐nitrobenzoate). Worm paramyosin chains have no sulfhydryl, so molecules comprising two worm chains or hybrid molecules comprising one chain of each type cannot crosslink. When run on sodium dodecyl sulfate polyacrylamide gel electrophoresis, therefore, the protein separates into two well‐resolved regions, one containing one‐chain species and the other two‐chain species. When the gels are scanned and quantitated, the hybrids show up as an increase in the fraction of material in the one‐chain band compared with the fraction in the blank solution. When renaturation is direct, we find that the fraction of renaturated molecules that are hybrids varies from ∼10% at 5°C to ∼5% at 25°C. These are judged to be nonequilibrium (quenched) values. When renaturation is by slow annealing, the equilibrium fraction hybrids are ∼4% and show a modest, but measurable, increase with increasing temperature. These data allow calculation of the equilibrium constantKhand standard free energy for the hybridization reaction: (1/2)CC + (½)WW = CW, in which C(W) stands for an α‐helical clam (worm) polypeptide chain. The temperature dependence gives the standard enthalpy and entropy of the reaction. We find ΔH h∞≃ 1800 cal mol−1and ΔH h∞≃ 1.4 cal mol−1K−1, using molarity concentration units and the infinitely dilute solution in NaCl/phosphate buffer as reference state. The possible molecular significance of these values is discussed, and it is concluded that the observed standard entropy arises essentially

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200507

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe formation and structure of four different Cu(II)–clupeine Z complexes have been studied using potentiometric and spectroscopic (ir and visible absorption, and CD) measurements. The results thus obtained indicate the presence of up to 8 binding sites in the pH range from 6.5 to 10.5. The spectroscopic evidence suggests that the strongest site available contains the α‐amino terminal and the adjacent peptide nitrogen, which bind to copper from pH 5 to 6.5 to form the first complex. The stability constant of this first complex has a value of (9.5 ± 0.9) × 103mol−11. From pH 6.5 to 8.5, two intervening guanidinium nitrogens of arginine residues occupy the two other corners of the coordination square, giving rise to the second complex. The other sites potentially available from pH 6.5 to 10.5 are formed by two amino nitrogens of arginine residues and two contiguous peptide nitrogens. The first intervene up to pH 8.5, forming the third complex, and the latter from this pH to 10.5, forming the fourth complex. Although the ligands intervening at sites 2–8 appear to be the same, the sites are by no means equivalent. The spectroscopic data enable one to distinguish three different types of bin

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200508

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

年代:1981

数据来源: WILEY

摘要:

AbstractThe unwinding of DNA strands in the presence of small concentrations of Mn2+ions (2 × 10−4−4 × 10−4M) has been studied. The process of unwinding is nonequilibrium; the DNA strands are gradually unwound at a constant temperature corresponding to the beginning of the melting curve. There is no true renaturation in the partially melted DNA. It is shown in the paper that these effects are due to the aggregation of the unwound DNA regions. The Mn2+ions are responsible for the binding of the unwound strands. The aggregation precludes renaturation, shifts the equilibrium towards the melted state, and causes slow unwinding at a constant temperature. The binding of denaturated regions seems to occur through the g

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200509

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

年代:1981

数据来源: WILEY

摘要:

AbstractCombined three‐ and four‐terminal AC bridge measurements have been made at frequencies from 10 Hz to 100 KHz on samples of DNA with different molecular weight in aqueous solution under varying conditions of DNA concentrations and added salt. A method is described for the separation of large quantities of DNA fractionated according to size. A complicated pattern of dependence of the specific dielectric increment on concentration is found, and the difficulties of comparing the results from sample to sample are discussed. The dielectric properties of the fractionated samples of DNA in aqueous solution are reported for solutions sufficiently dilute that specific dielectric increment is independent of concentration. The specific dielectric increment of the solutions (with concentration measured in moles of DNA molecules/liter) is found to increase as the square of the molecular weight. The results are compared with results of polyelectrolyte theories which deal explicitly with counterion fluctuations and interactions. The frequency dependence of the dispersion is much broader than for simple Debye relaxation. It is satisfactorily fitted by the empirical Cole–Cole circular are function and the breadth of the dispersion is found to be, if anything, less for the fractionated samples than for native DNA in sol

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200510

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

年代:1981

数据来源: WILEY

摘要:

AbstractA statistical‐mechanical model (a noninteracting local structure model) of folding and unfolding transition in globular proteins is described and a formulation is given to calculate the partition function. The process of transition is discussed in this model within the framework of equilibrium statistical mechanics. In order to clarify the range of applicability of such an approach, the characteristics of the folding and unfolding transition in globular proteins are analyzed from the statistical‐physical point of view. A theoretical advantage is pointed out in studying folding and unfolding processes taking place as conformational fluctuations in individual protein molecules under macroscopic equilibrium at the melting temperature. In this case, paths of folding and unfolding are shown to be identical in the statistical sense. A key to the noninteracting local structure model lies in the concept of local structures and the assumption of the absence of interactions between local structures. A local structure is defined as a continuous section of the chain which takes the same or similar local conformation as in the native conformation. The assumption of the absence of inter‐actions between local structures endows the model with the remarkable character that its partition function can be calculated exactly; thereby the equilibrium population of various conformations along the folding and unfolding paths can be discussed only by a knowledge of the folded native conform

ISSN:0006-3525    

DOI:10.1002/bip.1981.360200511

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

年代:1981

数据来源: WILEY