G-quadruplex DNA binding

Definition

Target type: molecularfunction

Binding to G-quadruplex DNA structures, in which groups of four guanines adopt a flat, cyclic Hoogsteen hydrogen-bonding arrangement known as a guanine tetrad. The stacking of guanine tetrads results in G-quadruplex DNA structures. G-quadruplex DNA can form under physiological conditions from some G-rich sequences, such as those found in telomeres, immunoglobulin switch regions, gene promoters, fragile X repeats, and the dimerization domain in the human immunodeficiency virus (HIV) genome. [PMID:16142245, PMID:9512530]

G-quadruplex DNA binding refers to the interaction of proteins or small molecules with G-quadruplex structures within DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences, characterized by stacked planar G-quartets, where four guanines are linked by Hoogsteen hydrogen bonds. These structures can adopt various topologies, including parallel, antiparallel, and hybrid forms, and are implicated in diverse cellular functions.

The molecular function of G-quadruplex DNA binding involves recognition and interaction of the binding entity with the G-quadruplex structure. This interaction can be driven by various factors, including:

* **Shape complementarity:** The binding entity may possess a shape that fits into the grooves or loops of the G-quadruplex, promoting specific binding.
* **Electrostatic interactions:** Positive charges on the binding entity can interact with the negatively charged phosphate backbone of the G-quadruplex.
* **Hydrogen bonding:** Specific amino acid residues or functional groups on the binding entity can form hydrogen bonds with the guanine bases within the G-quadruplex.
* **Hydrophobic interactions:** Non-polar residues on the binding entity can interact with the hydrophobic core of the G-quadruplex.
* **Stacking interactions:** Aromatic rings on the binding entity can stack onto the G-quartets within the G-quadruplex, contributing to stabilization.

These interactions can influence the stability, conformation, and function of the G-quadruplex, potentially regulating gene expression, telomere maintenance, and other cellular processes. For example, G-quadruplex binding proteins can modulate DNA replication, transcription, and translation by stabilizing or destabilizing G-quadruplex structures.

G-quadruplex DNA binding has significant implications in drug discovery and development. Small molecules that bind to G-quadruplexes have been investigated as potential therapeutics for various diseases, including cancer, neurodegenerative disorders, and infectious diseases. These molecules can target specific G-quadruplex structures involved in disease pathogenesis and exert therapeutic effects by modulating gene expression, inhibiting enzyme activity, or disrupting DNA replication.'
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Proteins (4)

Compounds (20)