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Crystal structure of a c-kit promoter quadruplex reveals the structural role of metal ions and water molecules in maintaining loop conformation

DOI: 10.1093/nar/gks023 DOI Help
PMID: 22287624 PMID Help

Authors: Dengguo Wei (University of London) , Gary N. Parkinson (University College London) , Anthony P. Reszka (University College London) , Stephen Neidle (University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research

State: Published (Approved)
Published: January 2012
Diamond Proposal Number(s): 1222

Open Access Open Access

Abstract: We report here the 1.62 Å crystal structure of an intramolecular quadruplex DNA formed from a sequence in the promoter region of the c-kit gene. This is the first reported crystal structure of a promoter quadruplex and the first observation of localized magnesium ions in a quadruplex structure. The structure reveals that potassium and magnesium ions have an unexpected yet significant structural role in stabilizing particular quadruplex loops and grooves that is distinct from but in addition to the role of potassium ions in the ion channel at the centre of all quadruplex structures. The analysis also shows how ions cluster together with structured water molecules to stabilize the quadruplex arrangement. This particular quadruplex has been previously studied by NMR methods, and the present X-ray structure is in accord with the earlier topology assignment. However, as well as the observations of potassium and magnesium ions, the crystal structure has revealed a highly significant difference in the dimensions of the large cleft in the structure, which is a plausible target for small molecules. This difference can be understood by the stabilizing role of structured water networks.

Journal Keywords: Crystallography; X-Ray; DNA; G-Quadruplexes; Magnesium; Models; Molecular; Nucleic; Potassium; Promoter; Genetic; Proto-Oncogene; Water

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 28/03/2012 14:25

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