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Titolo:
Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG]2 witha topoisomerase poison in the presence of Co2+ ions
Autore:
Thorpe, JH; Hobbs, JR; Todd, AK; Denny, WA; Charlton, P; Cardin, CJ;
Indirizzi:
Univ Reading, Dept Chem, Reading RG6 6AD, Berks, England Univ Reading Reading Berks England RG6 6AD eading RG6 6AD, Berks, England Univ Auckland, Fac Med & Hlth Sci, Auckland Canc Soc, Res Ctr, Auckland 1,New Zealand Univ Auckland Auckland New Zealand 1 oc, Res Ctr, Auckland 1,New Zealand Xenova PLC, Slough, Berks, England Xenova PLC Slough Berks EnglandXenova PLC, Slough, Berks, England
Titolo Testata:
BIOCHEMISTRY
fascicolo: 49, volume: 39, anno: 2000,
pagine: 15055 - 15061
SICI:
0006-2960(200012)39:49<15055:GSBAAD>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
POTENTIAL ANTITUMOR AGENTS; GEOMETRIC PARAMETERS; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; RESOLUTION; DERIVATIVES; COMPLEXES; GROOVE; MAD;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Cardin, CJ Univ Reading, Dept Chem, Reading RG6 6AD, Berks, England Univ Reading Reading Berks England RG6 6AD 6AD, Berks, England
Citazione:
J.H. Thorpe et al., "Guanine specific binding at a DNA junction formed by d[CG(5-BrU)ACG]2 witha topoisomerase poison in the presence of Co2+ ions", BIOCHEM, 39(49), 2000, pp. 15055-15061

Abstract

The structure of the duplex d[CG(5-BrU)ACG](2) bound to 9-bromophenazine-4-carboxamide has been solved through MAD phasing at 2.0 Angstrom resolution. It shows an unexpected and previously unreported intercalation cavity stabilized by the drug and novel binding modes of Co2+ ions at certain guanineN7 sites. For the intercalation cavity the terminal cytosine is rotated topair with the guanine of a symmetry-related duplex to create a pseudo-Holliday junction geometry, with two such cavities linked through the minor groove interactions of the N2/N3 guanine sites at an angle of 40 degrees, creating a quadruplex-like structure. The mode of binding of the drug is shown to be disordered, with the major conformations showing the side chain boundto the N7 position of adjacent guanines. The other end of the duplex exhibits a terminal base fraying in the presence of Co2+ ions linking symmetry-related guanines, causing the helices to intertwine through the minor groove. The stabilization of the structure by the intercalating drug shows that this class of compound may bind to DNA junctions as well as duplex DNA or tostrand-nicked DNA ('hemi-intercalated'), as in the cleavable complex. Thissuggests a structural basis for the dual poisoning of topoisomerase I and II enzymes by this family of drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 13:48:38