The structure of guanosine-thymidine mismatches in B-DNA at 2.5-A resolution.

Hunter, William N.; Brown, Tom; Kneale, Geoff; Anand, N.N.; Rabinovich, D.; Kennard, Olga

doi:10.1016/s0021-9258(18)61060-9

Cited by 170 publications

(75 citation statements)

References 33 publications

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“…Since the polyamides would be expected to be similarly hydrated and to release similar amounts of hydration water on complex formation, any differences in water released, among the complexes, would have to be due to differences in DNA hydration. Structural studies indicate that the T´G base pair adopts a wobble conformation with an unpaired free amino group of G that is strongly hydrated as part of the minor groove hydration matrix (12,45). On complex formation with f-ImImIm some of these tightly bound and highly ordered water molecules would be released from the T´G site to provide a favorable entropic contribution to complex formation.…”

Section: Discussionmentioning

confidence: 99%

“…This difference may be explained in terms of minor groove width. The groove of AT is unusually narrow (0.3±0.4 nm) ( 48), but it is wider in mixed DNA sequences (0.5±0.6 nm) (49) as well as at T´G base pairs (12). Since the thickness of one polyamide ring is~0.34 nm (50), the ®rst distamycin molecule can ®t snugly and make favorable van der Waals contacts with the walls of the minor groove in A 3 T 3 .…”

Section: Discussionmentioning

confidence: 99%

“…A T´G mismatch is often introduced by spontaneous deamination of 5-methylcytosine and can arise from errors in replication (10). Structural analysis of DNAs containing T´G mismatches, indicates that the mismatches adopt a wobble conformation and structural perturbations are mainly in the vicinity of the mismatch (11,12). NMR studies show that f-ImImIm forms an anti-parallel dimer in the DNA minor groove with a T´G mismatch site (5,6,13,14).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Energetic basis for selective recognition of T{middle dot}G mismatched base pairs in DNA by imidazole-rich polyamides

Lacy

Nguyen²,

Le³

et al. 2004

Nucleic Acids Research

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To complement available structure and binding results and to develop a detailed understanding of the basis for selective molecular recognition of T.G mismatches in DNA by imidazole containing polyamides, a full thermodynamic profile for formation of the T.G-polyamide complex has been determined. The amide-linked heterocycles f-ImImIm and f-PyImIm (where f is formamido group, Im is imidazole and Py is pyrrole) were studied by using biosensor-surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) with a T.G mismatch containing DNA hairpin duplex and a similar DNA with only Watson-Crick base pairs. Large negative binding enthalpies for all of the polyamide-DNA complexes indicate that the interactions are enthalpically driven. SPR results show slower complex formation and stronger binding of f-ImImIm to the T.G than to the match site. The thermodynamic analysis indicates that the enhanced binding to the T.G site is the result of better entropic contributions. Negative heat capacity changes for the complex are correlated with calculated solvent accessible surface area changes and indicate hydrophobic contributions to complex formation. DNase I footprinting analysis in a long DNA sequence provided supporting evidence that f-ImImIm binds selectively to T.G mismatch sites.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Energetic basis for selective recognition of T{middle dot}G mismatched base pairs in DNA by imidazole-rich polyamides

Lacy

Nguyen²,

Le³

et al. 2004

Nucleic Acids Research

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“…However, in the quest of understanding the mechanism of tautomerism involving conformations/structures known as 'excited states' (ESs) in biomolecules [9], various types of experimental and theoretical studies have been performed. Traditional spectroscopic techniques, such as, variable temperature NMR, 2-D IR [8,10], and X-ray crystallography [11][12][13][14][15][16] have been employed to characterize such tautomers. Theoretical studies by means of ab initio molecular orbital (MO), density functional theory (DFT) calculations [17][18][19][20], and molecular dynamics (MD) simulations [21][22][23] have been carried out in order to elucidate the transition mechanism.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that tautomerization of the G•T mispair depends significantly on the environment. For instance, G•T mispair adopt wobble configuration in case of Aand B-DNA [11,28] whereas, depending on the polymerase variants G•T mispair adopts WC-like structure in the closed state [14,29] and wobble structure in the open state [30]. Further, it has been reported that local microenvironment can modulate the wobble G•T WC-like enolic G•T equilibrium [31].…”

Section: Introductionmentioning

confidence: 99%

Multiscale Modeling of Wobble to Watson–Crick-Like Guanine–Uracil Tautomerization Pathways in RNA

Chandorkar

Raghunathan

Jaganade

2021

IJMS

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Energetically unfavorable Watson–Crick (WC)-like tautomeric forms of nucleobases are known to introduce spontaneous mutations, and contribute to replication, transcription, and translation errors. Recent NMR relaxation dispersion techniques were able to show that wobble (w) G•U mispair exists in equilibrium with the short-lived, low-population WC-like enolic tautomers. Presently, we have investigated the wG•U → WC-like enolic reaction pathway using various theoretical methods: quantum mechanics (QM), molecular dynamics (MD), and combined quantum mechanics/molecular mechanics (QM/MM). The previous studies on QM gas phase calculations were inconsistent with experimental data. We have also explored the environmental effects on the reaction energies by adding explicit water. While the QM-profile clearly becomes endoergic in the presence of water, the QM/MM-profile remains consistently endoergic in the presence and absence of water. Hence, by including microsolvation and QM/MM calculations, the experimental data can be explained. For the G•Uenol→ Genol•U pathway, the latter appears to be energetically more favorable throughout all computational models. This study can be considered as a benchmark of various computational models of wG•U to WC-like tautomerization pathways with and without the environmental effects, and may contribute on further studies of other mispairs as well.

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Non-Watson-Crick base associations in DNA and RNA revealed by single crystal x-ray diffraction methods: Mismatches, modified bases, and nonduplex DNA

Brown

Hunter

1997

Biopolymers

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The structure of guanosine-thymidine mismatches in B-DNA at 2.5-A resolution.

Cited by 170 publications

References 33 publications

Energetic basis for selective recognition of T{middle dot}G mismatched base pairs in DNA by imidazole-rich polyamides

Energetic basis for selective recognition of T{middle dot}G mismatched base pairs in DNA by imidazole-rich polyamides

Multiscale Modeling of Wobble to Watson–Crick-Like Guanine–Uracil Tautomerization Pathways in RNA

Non-Watson-Crick base associations in DNA and RNA revealed by single crystal x-ray diffraction methods: Mismatches, modified bases, and nonduplex DNA

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