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Titolo:
Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A center dot T-rich 14-mer duplex
Autore:
Parkinson, JA; Chen, Y; Murdoch, PD; Guo, ZJ; Berners-Price, SJ; Brown, T; Sadler, PJ;
Indirizzi:
Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland Univ Edinburgh Edinburgh Midlothian Scotland EH9 3JJ Midlothian, Scotland Griffith Univ, Sch Sci, Brisbane, Qld 4111, Australia Griffith Univ Brisbane Qld Australia 4111 , Brisbane, Qld 4111, Australia Univ Southampton, Southampton SO16 7PX, Hants, England Univ Southampton Southampton Hants England SO16 7PX 6 7PX, Hants, England
Titolo Testata:
CHEMISTRY-A EUROPEAN JOURNAL
fascicolo: 19, volume: 6, anno: 2000,
pagine: 3636 - 3644
SICI:
0947-6539(20001002)6:19<3636:SBODIB>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTICANCER DRUG CISPLATIN; INTRASTRAND CROSS-LINK; HMG-DOMAIN PROTEIN; EXCISION NUCLEASE; CRYSTAL-STRUCTURE; MAJOR ADDUCT; CIS-DIAMMINEDICHLOROPLATINUM(II); RECOGNITION; FORMS; OLIGONUCLEOTIDES;
Keywords:
antitumor agents; bioinorganic chemistry; DNA structures; NMR spectroscopy; platinum;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Sadler, PJ Univ Edinburgh, Dept Chem, W Mains Rd, Edinburgh EH9 3JJ, Midlothian, Scotland Univ Edinburgh W Mains Rd Edinburgh Midlothian Scotland EH93JJ
Citazione:
J.A. Parkinson et al., "Sequence-dependent bending of DNA induced by cisplatin: NMR structures of an A center dot T-rich 14-mer duplex", CHEM-EUR J, 6(19), 2000, pp. 3636-3644

Abstract

The NMR solution structure of the A . T rich DNA 14-mer duplex d(ATACATGGTACATA) . d(TATGTACCATGTAT) is reported. This is compared with the NMR structure of the same duplex intrastrand cross-linked at the d(G*pG*) site by cis-{Pt(NH3)(2)}(2+). derived from the anticancer drug cisplatin, The unmodified duplex has B-DNA geometry, but there is a large positive base-pair roll(roll angle 24 +/- 2 degrees) at the T9-A10 step on the 3' side of the central GG site. Platination of the DNA duplex causes the adjacent guanine bases to roll toward one another (roll angle 44 +/- 4 degrees), leading to an overall helix bend of 52 +/- 9 degrees, The platinum atom is displaced fromthe planes of the coordinated G7* and G8* by 0.8 Angstrom and 0.3 Angstrom. respectively. The minor groove opposite the platinum lesion is widened and flattened, with geometric parameters similar to those of A-form DNA, The unwinding of the helix at the platination site is 26 degrees. Platination causes the DNA duplex to bend toward the 3'-end (with respect to the G*G* strand), in contrast to G . C-rich structures reported previously, which bendtoward the 5'-end, This difference can be attributed to the predispositionof the A . T-rich duplex toward bending in this region. Protein recognition of bent platinated G*G* lesions may therefore exhibit a strong dependenceon the local DNA structure.

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Documento generato il 13/07/20 alle ore 20:20:59