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

   


Authors: Phan, A. T.; Kuryavyi, V.; Burge, S.; Neidle, S.; Patel, D. J.
Article Title: Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter
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. © 2007 American Chemical Society.
Keywords: gene sequence; promoter region; sequence analysis; proto-oncogene proteins c-kit; gene expression; dna; tumors; guanine; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; ligands; base pairing; models, molecular; solutions; molecular structure; nucleic acid conformation; protein folding; patient treatment; gene structure; oncogene c kit; topology; potassium ion; promoter regions (genetics); folding topology; g-quadruplex structures; intramolecular
Journal Title: Journal of the American Chemical Society
Volume: 129
Issue: 14
ISSN: 0002-7863
Publisher: American Chemical Society  
Date Published: 2007-04-11
Start Page: 4386
End Page: 4392
Language: English
DOI: 10.1021/ja068739h
PUBMED: 17362008
PROVIDER: scopus
PMCID: PMC4693632
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-34247160470&partnerID=40&md5=5a2eb5eff18e47a998d7201b0209847f
Notes: --- - "Cited By (since 1996): 90" - "Export Date: 17 November 2011" - "CODEN: JACSA" - "Source: Scopus"
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Anh Tuan Phan
    23 Phan
  2. Dinshaw J Patel
    477 Patel
  3. Vitaly V Kuryavyi
    27 Kuryavyi
Related MSK Work