J Am Chem Soc. 2007 Apr 11;129(14):4386-92. Epub 2007 Mar 16.

Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter.

Phan AT, Kuryavyi V, Burge S, Neidle S, Patel DJ.

Source

Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. phantuan@ntu.edu.sg

Abstract

The c-kit oncogene is an important target in the treatment of gastrointestinal tumors. A potential approach to inhibition of the expression of this gene involves selective stabilization of G-quadruplex structures that may be induced to form in the c-kit promoter region. Here we report on the structure of an unprecedented intramolecular G-quadruplex formed by a G-rich sequence in the c-kit promoter in K+ solution. The structure represents a new folding topology with several unique features. Most strikingly, an isolated guanine is involved in G-tetrad core formation, despite the presence of four three-guanine tracts. There are four loops: two single-residue double-chain-reversal loops, a two-residue loop, and a five-residue stem-loop, which contain base-pairing alignments. This unique structural scaffold provides a highly specific platform for the future design of ligands specifically targeted to the promoter DNA of c-kit.

PMID:: 17362008; [PubMed - indexed for MEDLINE]

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Structures reported by this article

Monomeric G-Dna Tetraplex From Human C-Kit Promoter

PDB: 2O3M

Source: Homo sapiens

Method: Solution Nmr

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