Crystal structures of A‐DNA duplexes

Wahl, Markus; Sundaralingam, M.

doi:10.1002/(sici)1097-0282(1997)44:1<45::aid-bip4>3.0.co;2-#

Cited by 117 publications

(113 citation statements)

References 89 publications

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“…But like that slogan, the sugar conformation mantra needs revision, because it ignores what we see in the crystallographic data. Whereas A DNA crystal structures show little deviation from C3Ј-endo sugar puckering (14,15), B DNA structures have a broad distribution of sugar puckers centered on C2Ј-endo but extending from C4Ј-exo to C3Ј-endo and beyond (9). Indeed, this greater flexibility of the B helix over A may make the B helix a better candidate for recognition by other macromolecules.…”

Section: Resultsmentioning

confidence: 98%

“…2. Typically, A and B DNA differ in the inclination of base pairs to the helical axis, lateral displacement of base pairs away from the helical axis, width and depth of the minor groove, deoxyribose ring conformation, and crystal packing (9,14,15,19,23).…”

Section: Resultsmentioning

confidence: 99%

“…G-tracts favor the A DNA helix conformation and, depending on the local water activity, can induce a B-to-A DNA transition (10)(11)(12)(13). Sequences with long G tracts usually crystallize as A DNA (14,15). The decamer CATGGC-CATG with a short 4-bp G-tract crystallizes as B DNA (16).…”

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confidence: 99%

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The structure of a stable intermediate in the A ↔ B DNA helix transition

Kopka

Dickerson

2000

Proc. Natl. Acad. Sci. U.S.A.

113

101

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The DNA dodecamer CATGGGCCCATG in a crystal structure of resolution 1.3 Å has a conformation intermediate between A and B DNA. This trapping of a stable intermediate suggests that the A and B DNA families are not discrete, as previously believed. The structure supports a base-centered rather than a backbone-centered mechanism for the A 7 B transition mediated by guanine tracts. Interconversion between A and B DNA provides another means for regulating protein-DNA recognition.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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The structure of a stable intermediate in the A ↔ B DNA helix transition

Kopka

Dickerson

2000

Proc. Natl. Acad. Sci. U.S.A.

113

101

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“…The higher rigidity of the D-Lys-containing PNA may be also related to the ability of LPD in discriminating mismatches in the target antiparallel DNA strand. It is known that the presence of mispairings in the double helices induces small distortions in the backbone conformation, leading to formation of the so-called ''wobble structures'' (35)(36)(37). The decrease in the backbone flexibility could hamper the conformational rearrangements necessary to accommodate the mispairs in the double helix.…”

Section: Discussionmentioning

confidence: 99%

Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a d -lysine-based chiral PNA–DNA duplex

Menchise

Simone

Tedeschi

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

151

164

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Peptide nucleic acids (PNAs) are oligonucleotide analogues in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton. They bind DNA and RNA with high specificity and selectivity, leading to PNA-RNA and PNA-DNA hybrids more stable than the corresponding nucleic acid complexes. The binding affinity and selectivity of PNAs for nucleic acids can be modified by the introduction of stereogenic centers (such as D-Lys-based units) into the PNA backbone. To investigate the structural features of chiral PNAs, the structure of a PNA decamer containing three D-Lys-based monomers (namely H-GpnTpnApnGpnAdlTdlCdlApnCpnTpn-NH2, in which pn represents a pseudopeptide link and dl represents a D-Lys analogue) hybridized with its complementary antiparallel DNA has been solved at a 1.66-Å resolution by means of a single-wavelength anomalous diffraction experiment on a brominated derivative. The D-Lys-based chiral PNA-DNA (LPD) heteroduplex adopts the so-called P-helix conformation. From the substantial similarity between the PNA conformation in LPD and the conformations observed in other PNA structures, it can be concluded that PNAs possess intrinsic conformational preferences for the P-helix, and that their flexibility is rather restricted. The conformational rigidity of PNAs is enhanced by the presence of the chiral centers, limiting the ability of PNA strands to adopt other conformations and, ultimately, increasing the selectivity in molecular recognition. P eptide nucleic acids (PNAs) are oligonucleotide mimics in which the sugar-phosphate backbone has been replaced by a pseudopeptide skeleton, composed of N-(2-aminoethyl)glycine units (1) (Fig. 1). Nucleobases are linked to this skeleton through a two-atom carboxymethyl spacer.PNAs bind DNA and RNA with high specificity and selectivity, forming Watson-Crick base pairs and leading to PNA-RNA and PNA-DNA hybrids that are more stable than the corresponding nucleic acid complexes (2). Because of their high thermal stability and resistance to proteases and nucleases, PNAs are ideal candidates as antisense or antigene therapeutic agents (3-6) and are currently used as powerful tools in molecular biology and in diagnostics (7).Three-dimensional structures have been determined for the major families of PNA complexes by different techniques. A PNA-RNA duplex (8) and a PNA-DNA duplex (9) were characterized by NMR in solution, whereas a (PNA) 2 -DNA triplex (10) and three PNA-PNA duplexes (11-13) were solved by x-ray crystallography. The structural analysis in solution of the PNA-DNA (9) and PNA-RNA duplexes (8) showed that PNA, when hybridized to RNA, adopts an A-like helix, whereas, when hybridized to a complementary DNA strand, it adopts a conformation that is different from both the A and the B forms. The crystal structure of the (PNA) 2 -DNA triplex (10) also showed helical parameters significantly different from those of canonical DNA or RNA helical forms, defining a type of helix, named the P-helix, characterized by a small twist angle, a large x-displacem...

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“…Steric effects associated with the amino groups of guanine in the minor groove of CpG B-DNA steps 59,69 or helical-twist/basepair-roll redistribution in alternating pyrimidine-purine A-RNA sequences belong to the best documented examples. 68,73,74 Nonparallel stacked bases are obviously very common in complex noncanonical RNA regions. When the bases are not parallel, the stacking geometry typically reflects a competition between a segment of the dimer where the monomers are locally unstacked and another segment where the monomers are sterically clashing.…”

Section: Introductionmentioning

confidence: 99%

Balance of Attraction and Repulsion in Nucleic-Acid Base Stacking: CCSD(T)/Complete-Basis-Set-Limit Calculations on Uracil Dimer and a Comparison with the Force-Field Description

Morgado

Jurečka

Svozil

et al. 2009

J. Chem. Theory Comput.

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Abstract:We have carried out reference quantum-chemical calculations for about 100 geometries of the uracil dimer in stacked conformations. The calculations have been specifically aimed at geometries with unoptimized distances between the monomers including geometries with mutually tilted monomers. Such geometries are characterized by a delicate balance between local steric clashes and local unstacking and had until now not been investigated using reference quantummechanics (QM) methods. Nonparallel stacking geometries often occur in nucleic acids and are of decisive importance, for example, for local conformational variations in B-DNA. Errors in the shortrange repulsion region would have a major impact on potential energy scans which were often used in the past to investigate local geometry variations in DNA. An incorrect description of such geometries may also partially affect molecular dynamics (MD) simulations in applications when quantitative accuracy is required. The reference QM calculations have been carried out using the MP2 method extrapolated to the complete basis-set limit and corrected for higher-order electron-correlation contributions using CCSD(T) calculations with a medium-sized basis set. These reference calculations have been used as benchmark data to test the performance of the DFT-D, SCS(MI)-MP2, and DFT-SAPT QM methods and of the AMBER molecular-mechanics (MM) force field. The QM methods show close to quantitative agreement with the reference data, albeit the DFT-D method tends to modestly exaggerate the repulsion of steric clashes. The force field in general also provides a good description of base stacking for the systems studied here. However, for geometries with close interatomic contacts and clashes, the repulsion effects are rather severely exaggerated. The discrepancy reported here should not affect the overall stability of MD simulations and qualitative applications of the force field. However, it may affect the description of subtle quantitative effects such as the local conformational variations in B-DNA. Preliminary calculations for two H-bonded uracil base pairs, including one with a C-H · · · O H-bond, indicate excellent performance of the tested QM methods for all intermonomer distances. The force field, on the other hand, is less satisfactory, especially in the repulsive regions.

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Crystal structures of A‐DNA duplexes

Cited by 117 publications

References 89 publications

The structure of a stable intermediate in the A ↔ B DNA helix transition

The structure of a stable intermediate in the A ↔ B DNA helix transition

Insights into peptide nucleic acid (PNA) structural features: The crystal structure of a d -lysine-based chiral PNA–DNA duplex

Balance of Attraction and Repulsion in Nucleic-Acid Base Stacking: CCSD(T)/Complete-Basis-Set-Limit Calculations on Uracil Dimer and a Comparison with the Force-Field Description

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