Document Detail


Small-molecule binding to the DNA minor groove is mediated by a conserved water cluster.
MedLine Citation:
PMID:  23276263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
High-resolution crystal structures of the DNA duplex sequence d(CGCGAATTCGCG)(2) complexed with three minor-groove ligands are reported. A highly conserved cluster of 11 linked water molecules has been found in the native and all 3 ligand-bound structures, positioned at the boundary of the A/T and G/C regions where the minor groove widens. This cluster appears to play a key structural role in stabilizing noncovalently binding small molecules in the AT region of the B-DNA minor groove. The cluster extends from the backbone phosphate groups along the mouth of the groove and links to DNA and ligands by a network of hydrogen bonds that help to maintain the ligands in position. This arrangement of water molecules is distinct from, but linked by, hydrogen bonding to the well-established spine of hydration, which is displaced by bound ligands. Features of the water cluster and observed differences in binding modes help to explain the measured binding affinities and thermodynamic characteristics of these ligands on binding to AT sites in DNA.
Authors:
DengGuo Wei; W David Wilson; Stephen Neidle
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  135     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-30     Completed Date:  2013-07-23     Revised Date:  2014-01-31    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1369-77     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Binding Sites
Crystallography, X-Ray
DNA / chemistry*
Models, Molecular
Molecular Structure
Molecular Weight
Water / chemistry*
Grant Support
ID/Acronym/Agency:
AI 064200/AI/NIAID NIH HHS; C129/A4489//Cancer Research UK; R01 AI064200/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
059QF0KO0R/Water; 9007-49-2/DNA
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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