Determination of the Number and Location of the Manganese Binding Sites of DNA Quadruplexes in Solution by EPR and NMR in the Presence and Absence of Thrombin

The present work is devoted to the analysis of the G-quadruplex DNA structure using the bioinformatics method. The interest towards quadruplex DNAs is determined by their involvement in the functioning of telomeres and onco-promoters as well as by the possibility to create on their basis aptamers and nanostructures. Here, we present an algorithm for a general analysis of the polymorphism of the G-quadruplex structure from the data bank PDB using original parameters. 74 structures were grouped according to the following parameters: the number of DNA strands, the number of G-quartets, and the location and orientation of the connecting loops. Two quantitative parameters were used to describe the quadruplex structure: the twist angle between two adjacent quartets (analogous to that for the complementary pair in the duplex DNA) and the quartet planarity (an original parameter). The distribution patterns of these values are specific for each group of quadruplex structures and are dependent upon the type of connecting loops used (diagonal, lateral or propeller). The tetramolecular loopless parallel quadruplex was used as a comparison template. The lateral loops introduce the strongest distortion into the structure of quadruplexes: the values of the twist angles are the lowest and are not typical for the other quadruplex groups. The loops of the diagonal type introduce much weaker deformation into quadruplexes; the structures with propeller loops are characterized by the optimum geometry of G-quartets. Hence, the correlation between the twist angle and the tension in the structure of quadruplex DNA is revealed.

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“…• 148D [40], 1C32 [41], 1C34 [41], 1C35 [41], 1C38 [41], 1QDF [42], 1QDH [42], 1RDE [43] – thrombin-binding DNA aptamer; …”

Section: Resultsmentioning

confidence: 99%

“…• 156D [53, 65], 1JPQ [25], 1L1H [66], 1QDI [42], 1QDK [42], 3EM2 [67], 3EQW [67], 3ERU [67], 3ES0 [67], 3ET8 [67], 3EUM [67], 2AKG [68], 1K4X [53], 1JRN [25], 2HBN [69], 3EUI [67] – telomeric DNA ( Oxytricha ); …”

Section: Resultsmentioning

confidence: 99%

Classification of G-Quadruplex DNA on the Basis of the Quadruplex Twist Angle and Planarity of G-Quartets

2010

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“…In this direction, recent works on EPR, infrared and other spectroscopic studies have extensively been carried out in a variety of biological systems [11][12][13][14][15]. In particular, a study on the binding of Mn 2+ to bovine pancreatic deoxyribonuclease I and DNA was studied by Jouve et al using EPR technique [11].…”

Section: Introductionmentioning

confidence: 99%

Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis

Narasimhulu¹,

Gopal²,

Rao³

et al. 2005

Biophysical Chemistry

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“…These structures also exhibit a range of groove widths and electrostatic potentials [32]. While the range of structural features for quadruplex DNA may not be as great as has been observed for proteins or RNA there is enough structural diversity [33] to suggest that quadruplex DNAs may well have regions that allow selective targeting of particular quadruplex structural types [1].…”

Section: Introductionmentioning

confidence: 99%

“…This approach is demonstrated here with the chair type quadruplex structure formed by the 15 mer d(GGTTGGTGTGGTTGG) that is often referred to as the thrombin binding aptamer, TBA. [31], [32], [38]–[40] An overview of the protocol is depicted in Figure 1. The extent of hydroxyl radical cleavage at a particular residue is proportional to the solvent accessibility of the sugar of that residue [41]–[44].…”

Section: Introductionmentioning

confidence: 99%

Finding and Characterizing the Complexes of Drug Like Molecules with Quadruplex DNA: Combined Use of an Enhanced Hydroxyl Radical Cleavage Protocol and NMR

2014

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Structural information on the complexes of drug like molecules with quadruplex DNAs can aid the development of therapeutics and research tools that selectively target specific quadruplex DNAs. Screening can identify candidate molecules that require additional evaluation. An enhanced hydroxyl radical cleavage protocol is demonstrated that can efficiently provide structural information on the complexes of the candidate molecules with quadruplex DNA. NMR methods have been used to offer additional structural information about the complexes as well as validate the results of the hydroxyl radical approach. This multi-step protocol has been demonstrated on complexes of the chair type quadruplex formed by the thrombin binding aptamer, d(GGTTGGTGTGGTTGG). The hydroxyl radical results indicate that NSC 176319, Cain’s quinolinium that was found by screening, exhibits selective binding to the two TT loops. The NMR results are consistent with selective disruption of the hydrogen bonding between T4 and T13 as well as unstacking of these residues from the bottom quartet. Thus, the combination of screening, hydroxyl radical footprinting and NMR can find new molecules that selectively bind to quadruplex DNAs as well as provide structural information about their complexes.

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Determination of the Number and Location of the Manganese Binding Sites of DNA Quadruplexes in Solution by EPR and NMR in the Presence and Absence of Thrombin

Cited by 67 publications

References 43 publications

Classification of G-Quadruplex DNA on the Basis of the Quadruplex Twist Angle and Planarity of G-Quartets

Classification of G-Quadruplex DNA on the Basis of the Quadruplex Twist Angle and Planarity of G-Quartets

Structural studies of the biomineralized species of calcified pancreatic stones in patients suffering from chronic pancreatitis

Finding and Characterizing the Complexes of Drug Like Molecules with Quadruplex DNA: Combined Use of an Enhanced Hydroxyl Radical Cleavage Protocol and NMR

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