Folding Pathways of Human Telomeric Type-1 and Type-2 G-Quadruplex Structures
| Autor: | Hiroshi Sugiyama, Tomoko Mashimo, Arivazhagan Rajendran, Hirotaka Yagi, Yuta Sannohe |
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| Rok vydání: | 2010 |
| Předmět: |
Base Sequence
Stereochemistry Chemistry Base pair Static Electricity Ab initio General Chemistry Molecular Dynamics Simulation Telomere G-quadruplex Biochemistry Catalysis G-Quadruplexes Folding (chemistry) Crystallography Molecular dynamics Colloid and Surface Chemistry Static electricity Alkane stereochemistry Humans Nucleic Acid Conformation Thermodynamics Binding site DNA Primers |
| Zdroj: | Journal of the American Chemical Society. 132:14910-14918 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja105806u |
| Popis: | We have investigated new folding pathways of human telomeric type-1 and type-2 G-quadruplex conformations via intermediate hairpin and triplex structures. The stabilization energies calculated by ab initio methods evidenced the formation of a hairpin structure with Hoogsteen GG base pairs. Further calculations revealed that the G-triplet is more stable than the hairpin conformation and equally stable when compared to the G-tetrad. This indicated the possibility of a triplex intermediate. The overall folding is facilitated by K(+) association in each step, as it decreases the electrostatic repulsion. The K(+) binding site was identified by molecular dynamics simulations. We then focused on the syn/anti arrangement and found that the anti conformation of deoxyguanosine is more stable than the syn conformation, which indicated that folding would increase the number of anti conformations. The K(+) binding to a hairpin near the second lateral TTA loop was found to be preferable, considering entropic effects. Stacking of G-tetrads with the same conformation (anti/anti or syn/syn) is more stable than mixed stacking (anti/syn and vice versa). These results suggest the formation of type-1 and type-2 G-quadruplex structures with the possibility of hairpin and triplex intermediates. |
| Databáze: | OpenAIRE |
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