Structure determination of [d(ATATATAUAT)]<sub>2</sub> via two‐dimensional NOE spectroscopy and molecular dynamics calculations

Kerwood, Deborah J.; Zon, Gerald; James, Thomas Leroy

doi:10.1111/j.1432-1033.1991.tb15947.x

Cited by 27 publications

(22 citation statements)

References 63 publications

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“…Propeller twist and buckle are variable and deviate substantially from classical B-DNA values of 0" and 4" respectively. The trend of a large negative propeller twist at the first three base pairs is similar to the observation of Mujeeb et al (1993) but some of the subsequent base pairs do have positive propeller twist in contrast to many NMR structures (Baleja et al, 1990;Kerwood et al, 1991 ;Kim et al, 1992;Stolarski et al, 1992;Mujeeb et al, 1993).…”

Section: Structural Featuressupporting

confidence: 50%

The Solution Conformation of a Trisdecanucleotide Containing the Consensus Binding Site of the dnaA Initiation Protein

Owen

Keniry

1994

European Journal of Biochemistry

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The solution structure of a trisdecanucleotide, d (CCTGTGGATAACA) . d (TGTTATCCACAGG) containing the consensus binding site of the dnaA initiation protein has been determined by twodimensional NMR techniques and restrained molecular dynamics calculations. Interproton distances were obtained by an iterative complete relaxation matrix algorithm, MARDIGRAS. During molecular dynamics runs, the backbone was restricted with the assistance of experimentally derived distance constraints. A family of refined structures with small painvise root-mean-square deviation values (~0 . 0 8 nm) was obtained. All but one of the pyrimidines were found to adopt the C1'-exo conformation while the purines were found to adopt the C2'-endo or C1'-exo conformation. The six-membered rings of the purines were found to stack over the six-membered rings of the pyrimidines while there is virtually no overlap of the pyrimidines over the purines. 5'-purine-purine-3' and 5'-pyrimidine-pyrimidine-3' stacking resembles the observed stacking of these bases in other NMR and X-ray structures of oligonucleotides. The final refined structure exhibited a small curvature and was slightly longer than canonical B-DNA. The variation of twist angle, proposed as a recognition element for proteins, exhibited symmetry about the centre of the consensus binding site.

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Section: Structural Featuressupporting

confidence: 50%

The Solution Conformation of a Trisdecanucleotide Containing the Consensus Binding Site of the dnaA Initiation Protein

Owen

Keniry

1994

European Journal of Biochemistry

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“…Conformational flexibility, thought to have induced a mixture of C2′-endo and C3′-endo conformations, due to a cross-link is also observed in the solution structure of a psoralen cross-linked DNA duplex with a d(GGGTACCC) sequence (45,46,48,49). The cross-link involves thymine residues in opposite strands at d(ApT)*d(ApT) sites, and these are flanked by G‚C Watson-Crick base pairs.…”

Section: Discussionmentioning

confidence: 94%

Solution Structure of a DNA Duplex Containing Mispair-Aligned N⁴C−Ethyl−N⁴C Interstrand Cross-Linked Cytosines

et al. 2002

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The solution structure of an interstrand cross-linked self-complementary oligodeoxynucleotide containing directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases was determined by molecular dynamics calculations guided by NMR-derived restraints. The undecamer d(CGAAACTTTCG)(2), where C represents directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases, serves as model for the cytotoxic cross-links formed by bifunctional alkylating agents used in cancer therapy. The structure of the duplex shows the cross-link protruding into the major groove. An increase in the diameter of the DNA at the pseudoplatform formed by the cross-linked residues creates an A-DNA characteristic hole in the central portion of the DNA. This results in a centrally underwound base step and a number of subsequent overwinding steps leading to an overall axis bend toward the major groove. The structure shows narrowing of both minor and major grooves in the proximity of the cross-link. The perturbation leads to preferential intrastrand base stacking, disruption of adjacent canonical (A.T) base pairing, and buckling of base pairs, the extent of which diminishes with progression away from the lesion site. Overall, the distortion induced by the cross-link spreads over three base pairs on the 5'- and 3'-sides of the cross-link.

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“…With MARDIGRAS, it is possible to compare experimental 2D NOE cross-peak intensities with values calculated for the starting structures as well as at each iteration in the MARDIGRAS algorithm (Kerwood et al, 1991). Various numerical indices could be used to evaluate the overall fit of experimental and calculated intensities.…”

Section: Assignment Of Proton Resonancesmentioning

confidence: 99%

A potential gene target in HIV-1: rationale, selection of a conserved sequence, and determination of NMR distance and torsion angle constraints

Mujeeb

Kerwin²,

Egan

et al. 1992

Biochemistry

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Recently, the capability for determining the high-resolution, sequence-dependent structure of oligonucleotides in solution via careful analysis of multidimensional NMR spectra and structure refinement procedures has been developed. Consequently, the rationale for selection of a genome sequence as a target for drug design based on the detailed three-dimensional structure of the target is presented. The concept is illustrated by the successful search for a highly conserved region of the HIV-1 genome's long terminal repeat which could serve as a molecular target. A compound which could selectively bind the target sequence could inhibit both RNA transcription from the integrated provirus and the reverse transcription process. Of 148 unique HIV-1 sequences examined, 147 exhibit a 21-base conserved sequence (nucleotides 70-90 in HIVHXB2R) in the R region of the long terminal repeat. The only exception, a minor constituent for one individual, has a change in the penultimate base. A 13 base pair duplex sequence, [d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT)], from this conserved region was selected and synthesized for NMR structure studies. Phase-sensitive proton two-dimensional nuclear Overhauser enhancement (2D NOE) and double-quantum-filtered correlation (2QF-COSY) spectra were obtained at 500 MHz for the DNA duplex. Exchangeable and nonexchangeable proton resonances were assigned. Quantitative assessments of the 2D NOE cross-peak intensities for different mixing times were carried out using conventional Fourier transform NMR and the maximum likelihood method (MLM). Distance constraints, along with upper and lower bounds, were obtained from the 2D NOE intensities using the iterative complete relaxation matrix algorithm MARDIGRAS. Distances entailing both exchangeable and nonexchangeable protons were determined: 7-11 experimental distance constraints per residue including interresidue and interstrand distances. Simulations of the scalar coupling effects manifest in 2QF-COSY cross-peaks by means of the program SPHINX/LINSHA were compared with experimental data to yield torsion angle constraints for the sugar rings. A single conformer was inadequate to describe any of the sugar puckers, but a rapid two-state equilibrium with one conformer strongly dominant (75-95%) provided a good fit of the 2QF-COSY cross-peaks. The sugar pucker of the major conformer exhibited significant variability for the various nucleotides but was roughly 2'-endo. Though derived independently and subject to different time-averaging effects, the 2QF-COSY and 2D NOE results are in accord.

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Structure determination of [d(ATATATAUAT)]₂ via two‐dimensional NOE spectroscopy and molecular dynamics calculations

Cited by 27 publications

References 63 publications

The Solution Conformation of a Trisdecanucleotide Containing the Consensus Binding Site of the dnaA Initiation Protein

The Solution Conformation of a Trisdecanucleotide Containing the Consensus Binding Site of the dnaA Initiation Protein

Solution Structure of a DNA Duplex Containing Mispair-Aligned N⁴C−Ethyl−N⁴C Interstrand Cross-Linked Cytosines

A potential gene target in HIV-1: rationale, selection of a conserved sequence, and determination of NMR distance and torsion angle constraints

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Structure determination of [d(ATATATAUAT)]2 via two‐dimensional NOE spectroscopy and molecular dynamics calculations

Cited by 27 publications

References 63 publications

The Solution Conformation of a Trisdecanucleotide Containing the Consensus Binding Site of the dnaA Initiation Protein

The Solution Conformation of a Trisdecanucleotide Containing the Consensus Binding Site of the dnaA Initiation Protein

Solution Structure of a DNA Duplex Containing Mispair-Aligned N4C−Ethyl−N4C Interstrand Cross-Linked Cytosines

A potential gene target in HIV-1: rationale, selection of a conserved sequence, and determination of NMR distance and torsion angle constraints

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Product

Resources

About

Structure determination of [d(ATATATAUAT)]₂ via two‐dimensional NOE spectroscopy and molecular dynamics calculations

Solution Structure of a DNA Duplex Containing Mispair-Aligned N⁴C−Ethyl−N⁴C Interstrand Cross-Linked Cytosines