2O3M

Monomeric G-DNA tetraplex from human C-kit promoter

Summary for 2O3M

• Entry DOI: 10.2210/pdb2o3m/pdb
• Related: 2A5P
• Descriptor: 5'-D(*AP*GP*GP*GP*AP*GP*GP*GP*CP*GP*CP*TP*GP*GP*GP*AP*GP*GP*AP*GP*GP*G)-3' (1 entity in total)
• Functional Keywords: g-tetrad;parallel g-quadruplex; edgewise, single-residue cha reversal, 5-nucleotide snap-back loops;broken strand topolog, dna
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 7028.52

Authors

Phan, A.T.,Kuryavyi, V.V.,Burge, S.,Neidle, S.,Patel, D.J. (deposition date: 2006-12-01, release date: 2007-05-22, Last modification date: 2023-12-27)

Primary citation

Phan, A.T.,Kuryavyi, V.V.,Burge, S.,Neidle, S.,Patel, D.J.
Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter.
J.Am.Chem.Soc., 129:4386-4392, 2007

PubMed 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.

PubMed: 17362008
DOI: 10.1021/ja068739h

Experimental method

SOLUTION NMR