Document Detail


Molecular basis for sequence-dependent induced DNA bending.
MedLine Citation:
PMID:  23355266     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
With a growing understanding of the microstructural variations of DNA, it has become apparent that subtle conformational features are essential for specific DNA molecular recognition and function. DNA containing an A-tract has a narrow minor groove and a globally bent conformation but the structural features of alternating AT DNA are less well understood. Several studies indicate that alternating AT sequences are polymorphic with different global and local properties from A-tracts. The mobility of alternating AT DNA in gel electrophoresis is extensively reduced upon binding with minor-groove binding agents such as netropsin. Although this suggests that such complexes are bent, similarly to A-tract DNA, direct evidence and structural information on AT DNA and the induced conformational change is lacking. We have used NMR spectroscopy and residual dipolar coupling together with restrained molecular-dynamics simulations to determine the solution structures of an alternating AT DNA segment, with and without netropsin, in order to evaluate the molecular basis of the binding-induced effects. Complex formation causes a significant narrowing of the minor groove and a pronounced change in bending, from a slight bend towards the major groove for the free DNA to a pronounced bend towards the minor groove in the complex. This observation demonstrates that conformational features and the inherent malleability of AT sequences are essential for specific molecular recognition and function. These results take the field of DNA structures into new areas while opening up avenues to target novel DNA sequences.
Authors:
Michael Rettig; Markus W Germann; Shuo Wang; W David Wilson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-25
Journal Detail:
Title:  Chembiochem : a European journal of chemical biology     Volume:  14     ISSN:  1439-7633     ISO Abbreviation:  Chembiochem     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-06     Completed Date:  2013-08-15     Revised Date:  2014-02-13    
Medline Journal Info:
Nlm Unique ID:  100937360     Medline TA:  Chembiochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  323-31     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Data Bank Information
Bank Name/Acc. No.:
PDB/2LWG;  2LWH
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
DNA / chemistry*,  metabolism
Ligands
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Netropsin / chemistry,  metabolism
Nucleic Acid Conformation
Grant Support
ID/Acronym/Agency:
AI 64200/AI/NIAID NIH HHS; R01 AI064200/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Ligands; 64B3O0RD7N/Netropsin; 9007-49-2/DNA
Comments/Corrections

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


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