Sequence specificity of quinoxaline antibiotics. 1. Solution structure of a 1:1 complex between triostin A and [d(GACGTC)]2 and comparison with the solution structure of the [N-MeCys3,N-MeCys7]TANDEM-[d(GATATC)]2 complex

Biochemistry ◽  
1994 ◽  
Vol 33 (41) ◽  
pp. 12386-12396 ◽  
Author(s):  
Kenneth J. Addess ◽  
Juli Feigon
Keyword(s):  
Solution Structure ◽  
Sequence Specificity ◽  
Triostin A

scholarly journals Bifunctional intercalation and sequence specificity in the binding of quinomycin and triostin antibiotics to deoxyribonucleic acid

1978 ◽  
Vol 173 (1) ◽  
pp. 115-128 ◽  
Author(s):  
J S Lee ◽  
M J Waring
Keyword(s):  
Binding Constant ◽  
Binding Constants ◽  
Sequence Specificity ◽  
Peptide Antibiotics ◽  
Naturally Occurring ◽  
Binding Isotherms ◽  
Triostin A ◽  
Specificity Pattern ◽  
Intercalating Agents ◽  
Binding Curves

Quinomycin C, triostin A and triostin C are peptide antibiotics of the quinoxaline family, of which echinomycin (quinomycin A) is also a member. They all remove and reverse the supercoiling of closed circular duplex DNA from bacteriophage PM2 in the fashion characteristic of intercalating drugs, and the unwinding angle at I 0.01 is, in all cases, almost twice that of ethidium. Thus, as with echinomycin, they can be characterized as bifunctional intercalating agents. For the triostins this conclusion has been confirmed by measurements of changes in the viscosity of sonicated rod-like DNA fragments; the helix extension was found to be almost double that expected for a simple monofunctional intercalation process. For triostin A, further evidence for bifunctionality was derived from the cross-over point of binding isotherms to nicked circular and closed circular bacteriophage-PM2DNA. Binding curves for the interaction of quinomycin C and triostin A with a variety of synthetic and naturally occurring nucleic acids were determined by solvent-partition analysis, but triostin C was too insoluble in aqueous solution to make this method applicable. For quinomycin C the highest binding constant was found with Micrococcus lysodeikticus DNA, and its pattern of specificity among natural DNA species was broadly similar to that of echinomycin, although the binding constants were 2–6 times as large. For triostin A the highest binding constant was again found for M. lysodeikticus DNA, but the specificity pattern was quite different from that of the quinomycins. In particular, triostin A bound better to poly(dA-dT) than to the poly(dG-dC) whereas this order was reversed for quinomycin C. There was also evidence that the binding to poly(dA-dT) might be co-operative in nature. No significant interaction could be detected with poly(dA).poly(dT) or with RNA from Escherichia coli. Poly(dG).poly(dC) gave variable results, depending on the source of the polymer. The different patterns of specificity displayed by the quinomycins and triostins are tentatively ascribed to differences in their conformations in solution.

Solution structure of the first three zinc fingers of TFIIIA bound to the cognate DNA sequence: determinants of affinity and sequence specificity

1997 ◽  
Vol 273 (1) ◽  
pp. 183-206 ◽  
Author(s):  
Deborah S. Wuttke ◽  
Mark P. Foster ◽  
David A. Case ◽  
Joel M. Gottesfeld ◽  
Peter E. Wright
Keyword(s):  
Dna Sequence ◽  
Solution Structure ◽  
Zinc Fingers ◽  
Sequence Specificity

scholarly journals Interaction between synthetic analogues of quinoxaline antibiotics and nucleic acids. Changes in mechanism and specificity related to structural alterations

1978 ◽  
Vol 173 (1) ◽  
pp. 129-144 ◽  
Author(s):  
J S Lee ◽  
M J Waring
Keyword(s):  
Binding Constant ◽  
Dimethyl Ester ◽  
Sedimentation Coefficient ◽  
Binding Constants ◽  
The Other ◽  
Sequence Specificity ◽  
Synthetic Dna ◽  
Cross Bridge ◽  
Naturally Occurring ◽  
Triostin A

The interaction with DNA of six chemically synthesized derivatives of the quinoxaline antibiotics was investigated. Five of the compounds bound only weakly to DNA or not at all; for these substances spectrophotometric measurements, sedimentation studies with closed circular duplex bacteriophage-PM2 DNA and thermal-denaturation profiles were used to determine limits fot the binding constants. No interaction could be detected with two products of degradation of echinomycin (quinomycin A), one of which, echinomycinic acid dimethyl ester, had the lactone linkages opened, whereas the other retained an intact octapeptide ring but had a broken cross-bridge. The other compounds studied were des-N-tetramethyl-triostin A (‘TANDEM’) and its derivatives. A derivative of ‘TANDEM’ IN WHICH benzyloxycarbonyl moieties replace both quinoxaline chromophores had binding constants to nucelic acids in the range 10(2)–10(3)-1, whereas no interaction could be detected for a benzyloxycarbonyl derivative that, in addition, had the cross-bridge broken. The derivative of ‘TANDEM’ with L-serine in place of D-serine in both positions showed no detectable interaction with Clostridium perfringens DNA, whereas the binding constant to poly(dA-dT) was approx 2 × 10(3)M-1. ‘TANDEM’ itself bound strongly to DNA, and the bathochromic and hypochromic shifts in its u.v.-absorption spectrum in the presence of DNA were similar to those seen with echinomycin. From the effect on the sedimentation coefficient of closed circular duplex bacteriophage-PM2 DNA the mechanism of binding was shown to involve bifunctional intercalation, typical of the naturally occurring quinoxaline antibiotics. Solvent-partition analysis was used to determine binding constants for the interaction between ‘TANDEM’ and a variety of natural and synthetic DNA species. The pattern of specificity thus revealed differed markedly from that previously found with the naturally occurring quinoxaline antibiotics. Most striking was the evident large preference for (A + T)-rich DNA species, in complete contrast with echinomycin and triostin A. The highest binding constant was found for poly(dA-dT), the interaction with which appeared highly co-operative in character. The conformations adopted by those quinoxaline compounds that bind strongly to DNA were examined withe aid of molecular models on the basis of results derived from n.m.r. and computer studies. It appears that the observed patterns of base-sequence specificity are determined, at least in part, by the structure and conformation of the sulphur-containing cross-bridge.

scholarly journals DNA recognition by quinoxaline antibiotics: use of base-modified DNA molecules to investigate determinants of sequence-specific binding of triostin A and TANDEM

1998 ◽  
Vol 330 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Christian BAILLY ◽  
J. Michael WARING
Keyword(s):  
Cyclic Peptide ◽  
Hydrophobic Interactions ◽  
Specific Binding ◽  
Amino Group ◽  
Sequence Specificity ◽  
Bonding Interaction ◽  
Modified Dna ◽  
Antibiotics Use ◽  
Triostin A ◽  
Groove Structure

The methodology of DNAase I footprinting has been adapted to investigate the sequence-specific binding of two quinoxaline drugs to DNA fragments containing natural and modified bases. In order to help comprehend the molecular origin of selectivity in the bis-intercalation of triostin A and TANDEM at CpG and TpA sites respectively, we have specifically examined the effect of the 2-amino group of guanine on their sequence specificity by using DNA in which that group has been either removed from guanine, added to adenine or both. Previous studies suggested that the recognition of particular nucleotide sequences by these drugs might be dependent upon the placement of the purine 2-amino group, serving as a positive or a negative effector for triostin A and TANDEM respectively. However, the footprinting data reported here indicate that this is not entirely correct, since they show that the 2-amino group of guanine is important for the binding of triostin A to DNA but has absolutely no influence on the interaction of TANDEM with TpA steps. Apparently the binding of triostin A to CpG sites is primarily due to hydrogen bonding interaction between the cyclic peptide of the antibiotic and the 2-amino group of guanine residues, whereas the selective binding of TANDEM to TpA sites is not hydrogen-bond driven and probably originates mainly from steric and/or hydrophobic interactions, perhaps involving indirect recognition of a suitable minor groove structure.

Solution structure of cytochrome b5 mutant (E44/48/56A/D60A) and its interaction with cytochrome c

2001 ◽  
Vol 268 (6) ◽  
pp. 1620-1630
Author(s):  
Yibing Wu ◽  
Yunhua Wang ◽  
Chengmin Qian ◽  
Jun Lu ◽  
Ercheng Li ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Solution Structure ◽  
Cytochrome B5

Sequence Specificity Despite Intrinsic Disorder: How a Disease-Associated Val/Met Polymorphism Shifts Tertiary Interactions in a Long Disordered Protein

2019 ◽  
Author(s):  
Ruchi Lohia ◽  
Reza Salari ◽  
Grace Brannigan
Keyword(s):  
Secondary Structure ◽  
Electrostatic Interactions ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Sequence Specificity ◽  
Intrinsically Disordered ◽  
Specific Effects ◽  
Heterogeneous Polymer ◽  
Non Local ◽  
Dynamics Simulations

<div>The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) encodes a hydrophobic-to-hydrophobic mutation at the midpoint of the prodomain of precursor brain-derived neurotrophic factor (BDNF), one of the earliest SNPs to be associated with neuropsychiatric disorders, for which the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica exchange molecular dynamics simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence.</div><div>The simulations were able to correctly reproduce the location of both local and non-local secondary changes due to the Val66Met mutation when compared with NMR spectroscopy. We find that the local structure change is mediated via entropic and sequence specific effects. We show that the highly disordered prodomain can be meaningfully divided into domains based on sequence alone. Monte Carlo simulations of a self-excluding heterogeneous polymer, with monomers representing each domain, suggest the sequence would be effectively segmented by the long, highly disordered polyampholyte near the sequence midpoint. This is qualitatively consistent with observed interdomain contacts within the BDNF prodomain, although contacts between the two segments are enriched relative to the self-excluding polymer. The Val66Met mutation increases interactions across the boundary between the two segments, due in part to a specific Met-Met interaction with a Methionine in the other segment. This effect propagates to cause the non-local change in secondary structure around the second methionine, previously observed in NMR. The effect is not mediated simply via changes in inter-domain contacts but is also dependent on secondary structure formation around residue 66, indicating a mechanism for secondary structure coupling in disordered proteins. </div>

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