Hydration of the Phosphate Group in Double-Helical DNA

Schneider, Bohdan; Patel, Ketan; Berman, Helen M.

doi:10.1016/s0006-3495(98)77686-6

Cited by 196 publications

(224 citation statements)

References 119 publications

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“…Because some of them cross-link with several duplexes, each duplex is in fact covered by about 120 water molecules. In general, hydration sites correspond to those described by Schneider et al (25,26). However, the water hydration of different residues is not regular.…”

Section: Organization Of Counterions: An Ionic Crystal Around the Trisupporting

confidence: 71%

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Solvent Organization in an Oligonucleotide Crystal

Soler-López¹,

Malinina²,

Subirana³

2000

Journal of Biological Chemistry

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We describe the crystal structure of d(GCGAATTCG) determined by x-ray diffraction at atomic resolution level (0.89 Å). The duplex structure is practically identical to that described at 2.05 Å resolution (Van Meervelt, L., Vlieghe, D., Dautant, A., Gallois, B., Pré cigoux, G., and Kennard, O. (1995) Nature 374, 742-744), however about half of the phosphate groups show multiple conformations. The crystal has three regions with different solvent structure. One of them contains several ordered Mg ؉2 ions and can be considered as an ionic crystal. A second region is formed by a network of ordered water molecules with a polygonal organization that binds three duplexes. The third region is formed by channels of solvent in which very few ordered solvent molecules are visible. The less ordered phosphates are found facing this channel. The latter region provides a view of DNA with highly movable charges, both negative phosphates and counterions, without a precise location.Two periods could be distinguished in the x-ray diffraction studies of DNA: the era of fiber diffraction of polymeric DNA/ polynucleotides and the time of single crystal x-ray structures of short fragments. The data available from fiber diffraction were limited and allowed no detailed analysis. The goal of DNA crystallography is, therefore, the study of detailed DNA structures. However, crystallographic data are also limited in some important aspects of DNA structure. For example, it is well known (1) that the solvent environment plays an important role in the conformational behavior and interactions of DNA. To study this feature in detail, it is necessary to work with x-ray data at atomic resolution level. Until recently, such data were available only for Z-DNA fragments. This situation is now changing. Synchrotron radiation of increasing power, together with better detectors and cryotechniques, make possible a third period of DNA crystallography: the epoch of high resolution DNA structures.We recently presented (2) a preliminary account of the structure of the B-DNA fragment (GCGAATTCG) solved at atomic resolution (0.89 Å). This structure had already been solved at 2.05-Å resolution (3, 4). In our previous analysis we described the water spine in the minor groove and compared it with related structures. Here we present a detailed analysis of the same oligonucleotide, which has multiple conformations in several parts of the phosphodiester backbone. We also describe the organization of the solvent, which in some regions shows well resolved water molecules, whereas in other regions it remains disordered, despite the fact that our crystals have been studied at 120 K. Thus, a frozen sample at atomic resolution, instead of showing a highly ordered duplex, demonstrates multiple conformations and regions of disordered solvent. MATERIALS AND METHODSCrystallization-The d(GCGAATTCG) nonamer was crystallized, using a batch method, in sitting drops containing 0.5 mM DNA duplex, 1 mM acridine-(Arg 4 ) drug-peptide aduct, 20 mM sodium cacodylate buffer, pH 7, 100 mM...

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Section: Organization Of Counterions: An Ionic Crystal Around the Trisupporting

confidence: 71%

“…The 19,26,31,and 38 Mg 2ϩ ions are well ordered and fully hydrated in the usual octahedral fashion. On the other hand, the 44, 49, and 52 Mg 2ϩ ions are partially disordered and not fully hydrated.…”

Section: Methodsmentioning

confidence: 99%

Solvent Organization in an Oligonucleotide Crystal

Soler-López¹,

Malinina²,

Subirana³

2000

Journal of Biological Chemistry

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“…26 Nucleic acids express charged oxygens (O 2 ) of phosphate groups that are spaced 0.5 to 0.7 nm apart. 30,31 These dimensions are similar to the known critical charge density of sulfated polysaccharides, in which sulfates are spaced about 0.5 nm apart along the carbohydrate backbone.27 Thus, the surface-exposed phosphate residues in RNA and DNA compounds most likely serve as binding partners for PF4. In fact, polysaccharides in which sulfate groups were substituted by phosphates were demonstrated to bind to PF4, indicating strong PF4-phosphate interaction.…”

mentioning

confidence: 73%

Complex formation with nucleic acids and aptamers alters the antigenic properties of platelet factor 4

Jaax

Krauel

Marschall

et al. 2013

Blood

133

110

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Key Points• PF4 binds to nucleic acids and thereby exposes the epitope to which anti-PF4/ heparin antibodies bind.• PF4/aptamer complexes can induce an immune response resembling heparin-induced thrombocytopenia.The tight electrostatic binding of the chemokine platelet factor 4 (PF4) to polyanions induces heparin-induced thrombocytopenia, a prothrombotic adverse drug reaction caused by immunoglobulin G directed against PF4/polyanion complexes. This study demonstrates that nucleic acids, including aptamers, also bind to PF4 and enhance PF4 binding to platelets. Systematic assessment of RNA and DNA constructs, as well as 4 aptamers of different lengths and secondary structures, revealed that increasing length and double-stranded segments of nucleic acids augment complex formation with PF4, while single nucleotides or single-stranded polyA or polyC constructs do not. Aptamers were shown by circular dichroism spectroscopy to induce structural changes in PF4 that resemble those induced by heparin. Moreover, heparin-induced anti-human-PF4/ heparin antibodies cross-reacted with human PF4/nucleic acid and PF4/aptamer complexes, as shown by an enzyme immunoassay and a functional platelet activation assay. Finally, administration of PF4/44mer-DNA protein C aptamer complexes in mice induced anti-PF4/aptamer antibodies, which cross-reacted with murine PF4/heparin complexes. These data indicate that the formation of anti-PF4/heparin antibodies in postoperative patients may be augmented by PF4/nucleic acid complexes. Moreover, administration of therapeutic aptamers has the potential to induce anti-PF4/polyanion antibodies and a prothrombotic diathesis. (Blood. 2013;122(2):272-281) IntroductionThe chemokine platelet factor 4 (PF4) is released from platelet a-granules during platelet activation 1 and binds, due to its high positive charge, to many negatively charged polyanions, including heparin. PF4 forms large multimolecular complexes with heparin that are highly immunogenic. 2,3 The resulting immunoglobulin G (IgG) antibodies are the cause of heparin-induced thrombocytopenia (HIT), a prothrombotic adverse drug effect. 4 In HIT, multimolecular complexes composed of PF4, heparin, and anti-PF4/heparin IgG cross-link platelet FcgIIa receptors, 5 triggering platelet activation, microparticle formation, and thrombin generation, with ;50% of affected patients developing thrombosis. 6 Recently, we showed that PF4 binds to polyanions on the surface of bacteria, thereby forming multimolecular complexes that are recognized by human anti-PF4/heparin antibodies. More specifically, we identified the PF4 binding site on gram-negative bacteria as the phosphate groups of lipid A. 7 Based on this observation, we hypothesized that nucleic acids might also form multimolecular complexes with PF4 because they also expose multiple negatively charged phosphate groups. This idea was fostered by previous findings that salmon sperm DNA could substitute heparin in HIT-IgG-induced platelet activation. 8Plasma levels of extracellular nucleic acids are re...

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“…The metals are fully integrated into the solvation shell, which is partially ordered [35][36][37]. On the basis of a MALDI-TOF analysis, the presence of Na + and K + cations in the p-isopropoxymodified sequences is highly unlikely, and these metal cations probably do not play any role in the conductivity of sequences 10 and 11.…”

Section: +mentioning

confidence: 99%

Conductivity of natural and modified DNA measured by scanning tunneling microscopy. The effect of sequence, charge and stacking

Kratochvílová¹,

Král²,

Bunček³

et al. 2008

Biophysical Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractThe conductivity of DNA covalently bonded to a gold surface was studied by means of the STM technique. Various single-and double-stranded 32-nucleotide-long DNA sequences were measured under ambient conditions so as to provide a better understanding of the complex process of chargecarrier transport in natural as well as chemically modified DNA molecules. The investigations focused on the role of several features of DNA structure, namely the role of the negative charge at the backbone phosphate group and the related complex effects of counterions, and of the stacking interactions between the bases in Watson-Crick and other types of base pairs. The measurements have indicated that the best conductor is DNA in its biologically most relevant double-stranded form with Watson-Crick base pairs and charged phosphates equilibrated with counterions and water. All the studied modifications, including DNA with non-Watson-Crick base pairs, the abasic form, and especially the form with phosphate charges eliminated by chemical modifications, lower the conductivity of natural DNA.

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Hydration of the Phosphate Group in Double-Helical DNA

Cited by 196 publications

References 119 publications

Solvent Organization in an Oligonucleotide Crystal

Solvent Organization in an Oligonucleotide Crystal

Complex formation with nucleic acids and aptamers alters the antigenic properties of platelet factor 4

Conductivity of natural and modified DNA measured by scanning tunneling microscopy. The effect of sequence, charge and stacking

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