X-ray crystallographic analysis of the hydration of A- and B-form DNA at atomic resolution

Egli, Martin; Tereshko, Valentina; Teplova, M.; Minasov, G.; Joachimiak, A.; Sanishvili, Ruslan; Weeks, Charles M.; Miller, Russ; Maier, Martin A.; An, Hongyu; Cook, P. Dan; Manoharan, Muthiah

doi:10.1002/(sici)1097-0282(1998)48:4<234::aid-bip4>3.0.co;2-h

Cited by 139 publications

(136 citation statements)

References 63 publications

Supporting

Mentioning

120

Contrasting

Order By: Relevance

“…DNA hydration has been extensively studied by several gravimetric, spectroscopic, osmotic stress, calorimetric, and scattering methods. [14][15][16][17][18][19][20][21][22][23][24] However, to our knowledge, simultaneous free energy and enthalpy data have not been reported previously.…”

Section: Discussionmentioning

confidence: 99%

The Hydration of a DNA−Amphiphile Complex

et al. 2004

View full text Add to dashboard Cite

We present measurements of isothermal DNA-hexadecyltrimethylammonium (DNACTA) complex and pure DNA hydration at 25°C using a sorption microcalorimeter. This calorimeter provides simultaneous measurement of (i) water activity (sorption isotherms) and (ii) the partial molar enthalpy of water as a function of water uptake. For pure DNA, hydration is exothermic over the studied concentration range and we find an approximately linear relation between the partial molar enthalpy and the partial molar free energy. A kink in the isotherm appears at 20.0 ( 0.3 water molecules per base pair for a water activity of 0.80, consistent with A-B transition of the DNA. There is no detectable heat effect associated with this transition. At low water contents, the hydration of the DNACTA (1:1) complex is exothermic as for the pure DNA, but after incorporation of the first 7.0 ( 0.1 water molecules, the enthalpy changes sign. At 22 water molecules per base pair, the enthalpy levels off to 2.7 ( 0.2 kJ/mol. In a separate experiment, the swelling limit for the DNACTA complex was found to be 27 ( 1 waters per base pair. The DNACTA complex is arranged in a hexagonal structure. We propose a model for the DNACTA complex based on the packing of the components in an electroneutral way consisting of six DNA helices, presumably in an A configuration, placed around a central CTA + cylinder. The hydration of the complex is seen as a balance between the attractive electrostatic interaction causing the formation of the complex and a repulsive component arising from a hexagonal deformation of CTA + cylinders. An important contribution to the partial molar enthalpy of water comes, in this interpretation, from the release of conformational constraints of the CTA ion alkyl chains.

show abstract

Section: Discussionmentioning

confidence: 99%

The Hydration of a DNA−Amphiphile Complex

et al. 2004

View full text Add to dashboard Cite

show abstract

“…For the ANA-modified B-form dodecamers, native B-DNA dodecamer search models in combination with the program CNS (40) were used. For the ANA-/2′-O-methyl-modified and FANA-/2′-O-methyl-modified DNA decamers, a highresolution native A-form structure was used as the MR search model (41), and the solutions were found by using EPMR (42). The structures of the modified B-form duplexes were initially refined with CNS and at a later stage with the program SHELX-97 (43).…”

Section: Methodsmentioning

confidence: 99%

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

Sarkhel

Wilds

et al. 2006

Biochemistry

Self Cite

View full text Add to dashboard Cite

2′-Deoxy-2′-fluoro-arabinonucleic acid (FANA) and arabinonucleic acid (ANA) paired to RNA are substrates of RNase H. The conformation of the natural DNA/RNA hybrid substrates appears to be neither A-form nor B-form. Consistent with this, the conformations of FANA and ANA were found to be intermediate between the A-and B-forms. However, FANA opposite RNA is preferred by RNase H over ANA, and the RNA affinity of FANA considerably exceeds that of ANA. By investigating the conformational boundaries of FANA and ANA residues in crystal structures of A-and B-form DNA duplexes at atomic resolution, we demonstrate that FANA and ANA display subtle conformational differences. The structural data provide insight into the structural requirements at the catalytic site of RNase H. They also allow conclusions with regard to the relative importance of stereoelectronic effects and hydration as modulators of RNA affinity.

show abstract

“…Phasing was carried out by the molecular replacement method using the program AMORE (26) as part of the CCP4 suite of crystallographic programs (27). An A-form DNA decamer of the same sequence GCGTATAGCG (28) was used as the search model. Promising solutions with good R-factors, reasonable correlation coefficients, and few short lattice contacts were found in both space groups.…”

Section: Methodsmentioning

confidence: 99%

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines

Diop-Frimpong

Prakash²,

Rajeev³

et al. 2005

Nucleic Acids Research

View full text Add to dashboard Cite

Substitution of oxygen atoms by sulfur at various locations in the nucleic acid framework has led to analogs such as the DNA phosphorothioates and 4′-thio RNA. The phosphorothioates are excellent mimics of DNA, exhibit increased resistance to nuclease degradation compared with the natural counterpart, and have been widely used as first-generation antisense nucleic acid analogs for applications in vitro and in vivo. The 4′-thio RNA analog exhibits significantly enhanced RNA affinity compared with RNA, and shows potential for incorporation into siRNAs. 2-Thiouridine (s2U) and 5-methyl-2-thiouridine (m5s2U) are natural nucleotide analogs. s2U in tRNA confers greater specificity of codon–anticodon interactions by discriminating more strongly between A and G compared with U. 2-Thio modification preorganizes the ribose and 2′-deoxyribose sugars for a C3′-endo conformation, and stabilizes heteroduplexes composed of modified DNA and complementary RNA. Combination of the 2-thio and sugar 2′-O-modifications has been demonstrated to boost both thermodynamic stability and nuclease resistance. Using the 2′-O-[2-(methoxy)ethyl]-2-thiothymidine (m5s2Umoe) analog, we have investigated the consequences of the replacement of the 2-oxygen by sulfur for base-pair geometry and duplex conformation. The crystal structure of the A-form DNA duplex with sequence GCGTAT*ACGC (T* = m5s2Umoe) was determined at high resolution and compared with the structure of the corresponding duplex with T* = m5Umoe. Notable changes as a result of the incorporation of sulfur concern the base-pair parameter ‘opening’, an improvement of stacking in the vicinity of modified nucleotides as measured by base overlap, and a van der Waals interaction between sulfur atoms from adjacent m5s2Umoe residues in the minor groove. The structural data indicate only minor adjustments in the water structure as a result of the presence of sulfur. The observed small structural perturbations combined with the favorable consequences for pairing stability and nuclease resistance (when combined with 2′-O-modification) render 2-thiouracil-modified RNA a promising candidate for applications in RNAi.

show abstract

X-ray crystallographic analysis of the hydration of A- and B-form DNA at atomic resolution

Cited by 139 publications

References 63 publications

The Hydration of a DNA−Amphiphile Complex

The Hydration of a DNA−Amphiphile Complex

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines

Contact Info

Product

Resources

About

X-ray crystallographic analysis of the hydration of A- and B-form DNA at atomic resolution

Cited by 139 publications

References 63 publications

The Hydration of a DNA−Amphiphile Complex

The Hydration of a DNA−Amphiphile Complex

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H,

Stabilizing contributions of sulfur-modified nucleotides: crystal structure of a DNA duplex with 2'-O-[2-(methoxy)ethyl]-2-thiothymidines

Contact Info

Product

Resources

About

2‘-Fluoroarabino- and Arabinonucleic Acid Show Different Conformations, Resulting in Deviating RNA Affinities and Processing of Their Heteroduplexes with RNA by RNase H^,