摘要:

AbstractMost carcinogens have been shown to be mutagens, and DNA adducts are formed when mutagenic/carcinogenic substances react with DNA. It is generally believed these adduclts (or their derivatives) induce misreplication events that result in mutations. Many of the more potently mutagenic substances are bulky and three‐dimensionally complex, such as the polycyclic aromatic hydrocarbons, aromatic amines, and aflatoxins; little is known about the mechanisms by which they induce mutations. Several theories exist and herein an additional mechanism is proposed by which bulky adducts might induce mutations at GC base pairs. Molecular modeling in conjunction with molecular mechanical calculation is used to assess if the mutagen/carcinogen moiety of the adduct might be able to shift the position of the base moiety of the adduct in such a way that misreplication events might be facilitated. This mechanism is referred to as adduct‐induced base‐shift, and two classes appeared possible; adduct‐induced base‐wobble and adduct‐induced base‐rotation. The latter has been proposed previously. By addut‐induced, base‐wobble, the mutagen/carcinogen moiety of the adduct induces a shift in the position of the base moiety of the adduct with respect to the helix axis, which might facilitate mispairing events that are reminisent of non‐Watson/Crick pairing that occurs at the wobble base of tRNA during translation. For example, in some guanine adducts, the guanine appears more thymine‐like, which might facilitate G. A mispairing and thereby ultimately GC to TA transversion mutations. Adduct‐induced base‐rotation involves the rotation of the adducted base from theantito thesynconformation and a variety of mispa

ISSN:0006-3525    

DOI:10.1002/bip.360280502

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe have applied the formalism developed previously for the kinetics of domain‐localized reaction [S. Mazur and M. T. Record, Jr. (1986)Biopolymers25, 985–1008] to describe complex mechanisms of association of a protein with a specific site on a large DNA molecule also containing many nonspecific binding sites. These nonspecific sites participate in the mechanism of formation of the specific complex through competitive binding and the facilitating mechanisms of sliding and transfer. The effects of localizing the sites in a domain are represented by a simple algebraic expression, and the sequence of interactions within the domain are described by equations closely related to a conventional, homogeneous solution mechanism. We apply this formalism to examine the interplay between sliding and direct transfer in domain‐localized interactions in general and in thelacrepressor‐lacoperator interaction in particular. Experimental investigation of the effect of the molecular location of the specific site (e.g., end vs middle of the polymer chain) on the kinetics of association may allow the contributions of sliding and direct transfer to be r

ISSN:0006-3525    

DOI:10.1002/bip.360280503

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

年代:1989

数据来源: WILEY

摘要:

AbstractThe rotational relaxation times of nonpolymerizable skeletal and smooth muscle tropomyosin were measured by analysis of the decay of the zero‐field birefringence at different temperatures and salt concentrations. Skeletal tropomyosin in solution is equally well modeled as a rigid rod or as a semiflexible rod with a persistence length of 150 nm. Smooth muscle tropomyosin does not fit the rigid rod model but is well approximated by a semiflexible rod model with a persistence length of 55 nm. The results indicate that smooth muscle tropomyosin is either a more flexible molecule than skeletal muscle tropomyosin or is a curved structure with an end‐to‐end length shorter than the coiled‐coil contour length. Smooth muscle tropomyosin controls the actomyosin ATPase differently from skeletal muscle tropomyosin and it had been suggested that the reason is because it is more rigid; clearly, another explanation must be

ISSN:0006-3525    

DOI:10.1002/bip.360280504

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

年代:1989

数据来源: WILEY

摘要:

AbstractOligo‐DNAs are synthesized on a solid support using the 9‐fluorenylmethyloxycarbonyl group as a 5′‐OH base labile protection. The synthesis of the pure protected nucleotides, a relevant phosphoramidite‐type strategy of coupling, and the optimization of the deprotection steps are described. This new synthetic method is an alternative to the standard protocol that avoids acidic c

ISSN:0006-3525    

DOI:10.1002/bip.360280505

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

年代:1989

数据来源: WILEY

摘要:

AbstractElectrostatic potentials around DNA are obtained by solving the nonlinear Poisson‐Boltzmann (PB) equation. The detailed charge distribution of the DNA and the different polarizabilities of the macromolecule and solvent are included explicitly in the calculations. The PB equation is solved using extensions of a finite difference approach applied previously to proteins. Electrical potentials and ion concentrations are compared to those obtained with simpler models. It is found that the shape of the dielectric boundary between the macromolecule and solvent has significant effects on the calculated potentials near the surface, particularly in the grooves. Sequence‐specific patterns are found, the most surprising result being the existence of positive regions of potential near the bases in both the major and minor grooves. The effect of solvent and ionic atmosphere screening of phosphate‐phosphate repulsions is studied, and an effective dielectric function, appropriate for molecular mechanics simulations, is de

ISSN:0006-3525    

DOI:10.1002/bip.360280506

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

年代:1989

数据来源: WILEY

摘要:

AbstractAn estimation of the thermodynamic effects of a charged random coil, which is attached either to the N‐ or C‐terminus of polyalanine, upon α‐helix stability is attempted. A temperature‐induced helix‐coil transition of Ala20Lys20Phe and Lys20Ala20Phe was studied under various conditions of salt concentration and pH. By combining the results with previous ones for Ala20Glu20Phe and Glu20Ala20Phe, which have opposite electric charges to the present system [S. Ihara et al. (1982)Biopolymers21, 131–145], the free energy of the coil to helix transition of the polyalanine block could be separated into two terms—one term for the electrostatic interaction of electric charges in the random‐coil block with the α‐helix dipole, and a second term for the intrinsic stability of the helix. The first term indicates the significance of the helix dipole‐charge interactions, which affects the helix stability depending on the attaching side of the charged block and on the sign of the charges. This clearly shows the anisotropic stability of the α‐helix. Furthermore, analysis of the dependence of these thermodynamic quantities on salt concentrations showed, assuming that the effect of the attached electric charges was symmetric (in other words, the absolute values of the electrostatic interaction terms were independent of the sign of electric charges), that the intrinsic stability of the α‐helix was dependent on which side of the helix was attached to the random coil: a random coil attached to the N‐terminus of the α‐helix had little effect while that attached to a C‐terminal si

ISSN:0006-3525    

DOI:10.1002/bip.360280507

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

年代:1989

数据来源: WILEY

摘要:

AbstractMeasurements of small‐angle x‐ray scattering have been made on films prepared from fine and coarse (i.e., formed at high and low, respectively, pH and ionic strength) clots of bovine fibrin by osmotic shrinkage or compression in one dimension. Intensity profiles were obtained with pinhole geometry on films stretched up to a stretch ratio of 1.43. In unstretched coarse films, repeat spacings were seen at about 245, 120, and 77–80 Å. These peaks can probably be identified with the first, second, and third orders of the well‐known fibrin repeat of 225 Å. In unstretched fine films, only the 77–80 Å spacing was seen. In this case, the first two orders may be weak because the half‐staggered arrangement of monomer units giving rise to the 225 Å reflection is not reinforced by lateral aggregation of protofibrils; the third order may be strong since the molecular subdomains appear to divide the repeat roughly into thirds. After stretching, the 77–80 Å spacing persisted in the meridional direction but almost disappeared in the equatorial. Experiments on unstretched films prepared with ancrod substituted for thrombin ga

ISSN:0006-3525    

DOI:10.1002/bip.360280508

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

年代:1989

数据来源: WILEY

摘要:

AbstractWe have used Raman scattering to study the water O‐H stretching modes at ∼ 3450 and ∼ 3220 cm−1in DNA films as a function of relative humidity (r.h.). The intensity of the 3220‐cm−1band vanishes as the r.h. is decreased from 98% to around 80%, which indicates that the hydrogen‐bond network of water is disrupted in the primary hydration shell (which therefore cannot have an “ice‐like” structure). The number of water molecules in the primary hydration shell was determined from the intensity of the ∼ 3200‐cm−1band as about 30 water molecules per nucleotide pair. The ∼ 3400‐cm−1O‐H stretch band was used for determining the total water content, and this band persists at 0% r.h., implying that 5–6 tightly bound water molecules per nucleotide pair remain. The frequency of the ∼ 3400‐cm−1O‐H stretch mode is lower by 30 to 45 cm−1in the primary hydration shell compared to free water. The water content as a function of r.h. obtained from these experiments agrees with gravimetric measurements. The disappearance of the ∼ 3200‐cm−1band and the shift of the ∼ 3400‐cm−1O‐H stretch band prov

ISSN:0006-3525    

DOI:10.1002/bip.360280509

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

年代:1989

数据来源: WILEY

ISSN:0006-3525    

DOI:10.1002/bip.360280501

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

年代:1989

数据来源: WILEY