Linked Life Data

10891271

Source:http://linkedlifedata.com/resource/pubmed/id/10891271

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2000-8-15
pubmed:abstractText
Recognition and biochemical processing of DNA requires that proteins and other ligands are able to distinguish their DNA binding sites from other parts of the molecule. In addition to the direct recognition elements embedded in the linear sequence of bases (i.e. hydrogen bonding sites), these molecular agents seemingly sense and/or induce an "indirect" conformational response in the DNA base-pairs that facilitates close intermolecular fitting. As part of an effort to decipher this sequence-dependent structural code, we have analyzed the extent of B-->A conformational conversion at individual base-pair steps in protein and drug-bound DNA crystal complexes. We take advantage of a novel structural parameter, the position of the phosphorus atom in the dimer reference frame, as well as other documented measures of local helical structure, e.g. torsion angles, base-pair step parameters. Our analysis pinpoints ligand-induced conformational changes that are difficult to detect from the global perspective used in other studies of DNA structure. The collective data provide new structural details on the conformational pathway connecting A and B-form DNA and illustrate how both proteins and drugs take advantage of the intrinsic conformational mechanics of the double helix. Significantly, the base-pair steps which exhibit pure A-DNA conformations in the crystal complexes follow the scale of A-forming tendencies exhibited by synthetic oligonucleotides in solution and the known polymorphism of synthetic DNA fibers. Moreover, most crystallographic examples of complete B-to-A deformations occur in complexes of DNA with enzymes that perform cutting or sealing operations at the (O3'-P) phosphodiester linkage. The B-->A transformation selectively exposes sugar-phosphate atoms, such as the 3'-oxygen atom, ordinarily buried within the chain backbone for enzymatic attack. The forced remodeling of DNA to the A-form also provides a mechanism for smoothly bending the double helix, for controlling the widths of the major and minor grooves, and for accessing the minor groove edges of individual base-pairs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CAGCTG-specific type II..., http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Directed DNA Polymerase, http://linkedlifedata.com/resource/pubmed/chemical/Deoxyribonucleases, Type II..., http://linkedlifedata.com/resource/pubmed/chemical/Endodeoxyribonucleases, http://linkedlifedata.com/resource/pubmed/chemical/GATATC-specific type II..., http://linkedlifedata.com/resource/pubmed/chemical/HIV Reverse Transcriptase, http://linkedlifedata.com/resource/pubmed/chemical/I-Ppo endonuclease, http://linkedlifedata.com/resource/pubmed/chemical/Ligands, http://linkedlifedata.com/resource/pubmed/chemical/Transposases
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
819-40
pubmed:dateRevised
2008-8-29
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
A-form conformational motifs in ligand-bound DNA structures.
pubmed:affiliation
Department of Chemistry, Wright-Rieman Laboratories, Rutgers, the State University of New Jersey, 610 Taylor Road, Piscataway, NJ, 08854-8087, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't