The Definition of Generalized Helicoidal Parameters and of Axis Curvature for Irregular Nucleic Acids

Lavery, R.; Sklenar, Heinz

doi:10.1080/07391102.1988.10506483

Cited by 901 publications

(737 citation statements)

References 24 publications

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“…Since the reference frames used in 3DNA roughly coincide with the frames used in CompDNA 43 and Curves 44,45 , the 3DNA base-pair and basepair step parameters closely resemble the values determined with CompDNA and the local parameters from Curves (except when DNA is highly kinked and the Curves values tend to be larger 29 ). The discrepancies are more pronounced with programs, such as SCHNAaP/ CEHS [26][27][28] , Newhelix/Freehelix 42 , and RNA 40 , that employ very different reference frames 30 .…”

Section: Relationship To Other Programsmentioning

confidence: 56%

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

2008

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We present a set of protocols showing how to use the 3DNA suite of programs to analyze, rebuild, and visualize three-dimensional nucleic-acid structures. The software determines a wide range of conformational parameters, including the identities and rigid-body parameters of interacting bases and base-pair steps, the nucleotides comprising helical fragments, the area of overlap of stacked bases, etc. The reconstruction of three-dimensional structure takes advantage of rigorously defined rigid-body parameters, producing rectangular block representations of the nucleic-acid bases and base pairs and all-atom models with approximate sugar-phosphate backbones. The visualization components create vector-based drawings and scenes that can be rendered as raster-graphics images, allowing for easy generation of publication-quality figures. The utility programs use geometric variables to control the view and scale of an object, for comparison of related structures. The commands run in seconds even for large structures. The software and related information are available at http://3dna.rutgers.edu/.

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Section: Relationship To Other Programsmentioning

confidence: 56%

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

2008

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“…We used CURVES, an algorithm designed to extract the measure of DNA groove dimensions and nucleobase stacking geometries (43)(44)(45). CURVES models the DNA backbone with a cubic spline interpolation of phosphate positions, allowing for continuous groove measurements throughout most of the structured DNA in the complex, albeit this treatment does not define groove dimensions at the DNA ends.…”

Section: Dna Groove Dimensions In Hox-exd/pbx1 Structuresmentioning

confidence: 99%

Targeted Chemical Wedges Reveal the Role of Allosteric DNA Modulation in Protein−DNA Assembly

et al. 2008

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The cooperative assembly of multiprotein complexes results from allosteric modulations of DNA structure as well as direct intermolecular contacts between proteins. Such cooperative binding plays a critical role in imparting exquisite sequence specificity on the homeobox transcription factor (Hox) family of developmental transcription factors. A well-characterized example includes the interaction of Hox proteins with extradenticle (Exd), a highly conserved DNA binding transcription factor. Although direct interactions are important, the contribution of indirect interactions toward cooperative assembly of Hox and Exd remains unresolved. Here we use minor groove binding polyamides as structural wedges to induce perturbations at specific base steps within the Exd binding site. We find that allosteric modulation of DNA structure contributes nearly 1.5 kcal/mol to the binding of Exd to DNA, even in the absence of direct Hox contacts. In contrast to previous studies, the sequence-targeted chemical wedges reveal the role of DNA geometry in cooperative assembly of Hox-Exd complexes. Programmable polyamides may well serve as general probes to investigate the role of DNA modulation in the cooperative and highly specific assembly of other protein-DNA complexes.The physical basis of DNA sequence recognition by its ligands (proteins or small molecules) has been investigated in great detail over the years, and several underlying principles have been defined (1-3). The main contributors to the specificity of DNA sequence recognition are interactions between protein side chains and the edges of the base pairs in the cognate DNA site. Efforts to rationally redesign these direct interactions have yielded some exciting successes (4-8). A major limitation of focusing on re-engineering direct interactions, however, is that recognition of sequence-dependent structural properties of DNA and other modes of indirect readout are also critical specificity determinants (9-15). Often a combination of direct and indirect interactions governs exquisite DNA sequence specificity displayed by its ligands (9,11,(14)(15)(16)(17)(18)(19)(20)(21)(22). Specificity in molecular recognition is also achieved by cooperative binding of multiple proteins to closely appositioned DNA sequences (23). Binding of one protein to its DNA cognate site in the enhancer can alter DNA structure and conformational flexibility of a juxtaposed site, thus allosterically improving the energetics

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“…Helicoidal analysis suggested a 10° decrease of the twist angle between base pairs X 6 ·T 17 and Y 7 ·T 16 , resulting in an unwinding of the duplex (89). An approximate 10° bending of the cross-linked duplex was calculated using the program CURVES (90,91), probably a consequence of placing the two hydroxyl groups at C β and C γ in the anti conformation with respect to the C β -C γ bond, which did not allow the four carbon cross-link to exist in the extended chain conformation. …”

Section: Structure Of the (Ss)-bd-(61-23) Cross-linked Adductmentioning

confidence: 99%

Structure of the 1,4-Bis(2‘-deoxyadenosin-N⁶-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

Merritt

Nechev

et al. 2007

Chem. Res. Toxicol.

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The 1,4-bis(2′-deoxyadenosin-N 6 -yl)-2S,3S-butanediol intra-strand DNA cross-link arises from bisalkylation of tandem N 6 -dA sites in DNA by R,R-butadiene diepoxide (BDO 2 ). The oligodeoxynucleotide 5′-d(C 1 G 2 G 3 A 4 C 5 X 6 Y 7 G 8 A 9 A 10 G 11 )-3′·5′-d (C 12 T 13 T 14 C 15 T 16 T 17 G 18 T 19 C 20 C 21 G 22 )-3′ contains the BDO 2 cross-link between the second and third adenines of the codon 61 sequence (underlined) of the human N-ras protooncogene and is named the (S,S)-BD-(61-2,3) cross-link (X,Y = cross-linked adenines). NMR analysis reveals that the cross-link is oriented in the major groove of duplex DNA. Watson-Crick base pairing is perturbed at base pair X 6 ·T 17 , whereas base pairing is intact at base pair Y 7 ·T 16 . The cross-link appears to exist in two conformations, in rapid exchange on the NMR time scale. In the first conformation, the β-OH is predicted to form a hydrogen bond with T 16 O 4 , whereas in the second, the β-OH is predicted to form a hydrogen bond with T 17 O 4 . In contrast to the (R,R)-BD-(61-2,3) cross-link in the same sequence [Merritt, W.K., Nechev, L.V., Scholdberg, T.A., Dean, S.M., Kiehna, S.E., Chang, J.C., Harris, T.M., Harris, C.M., Lloyd, R.S., and Stone, M.P. (2005) Biochemistry 44, 10081-10092], the anti conformation of the two hydroxyl groups at C β and C γ with respect to the C β -C γ bond results in a decreased twist between base pairs X 6 ·T 17 and Y 7 ·T 16 , and an approximate 10° bending of the duplex. These conformational differences may account for the differential mutagenicity of the (S,S)-and (R,R)-BD-(61-2,3) cross-links, and suggest that stereochemistry plays a role in modulating biological responses to these cross-links [Kanuri, M., Nechev, L. V., Tamura, P. J., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2002) Chem. Res. Toxicol. 15, 1572-1580.

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The Definition of Generalized Helicoidal Parameters and of Axis Curvature for Irregular Nucleic Acids

Cited by 901 publications

References 24 publications

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

Targeted Chemical Wedges Reveal the Role of Allosteric DNA Modulation in Protein−DNA Assembly

Structure of the 1,4-Bis(2‘-deoxyadenosin-N⁶-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

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The Definition of Generalized Helicoidal Parameters and of Axis Curvature for Irregular Nucleic Acids

Cited by 901 publications

References 24 publications

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

3DNA: a versatile, integrated software system for the analysis, rebuilding and visualization of three-dimensional nucleic-acid structures

Targeted Chemical Wedges Reveal the Role of Allosteric DNA Modulation in Protein−DNA Assembly

Structure of the 1,4-Bis(2‘-deoxyadenosin-N6-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

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Structure of the 1,4-Bis(2‘-deoxyadenosin-N⁶-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence