THE MOLECULAR-STRUCTURE OF A 4'-EPIADRIAMYCIN COMPLEX WITH D(TGATCA) AT 1.7-ANGSTROM RESOLUTION - COMPARISON WITH THE STRUCTURE OF 4'-EPIADRIAMYCIN D(TGTACA) AND D(CGATCG) COMPLEXES

被引:22
作者
DESTAINTOT, BL
GALLOIS, B
BROWN, T
HUNTER, WN
机构
[1] UNIV MANCHESTER,DEPT CHEM,OXFORD RD,MANCHESTER M13 9PL,LANCS,ENGLAND
[2] UNIV BORDEAUX 1,CRISTALLOG LAB,CNRS,URA 144,F-33405 TALENCE,FRANCE
[3] UNIV EDINBURGH,DEPT CHEM,EDINBURGH EH8 9YL,MIDLOTHIAN,SCOTLAND
基金
英国惠康基金;
关键词
D O I
10.1093/nar/20.14.3561
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The structure of the complex between d(TGATCA) an the anthracycline 4'-epiadriamycin has been determined by crystallographic methods. The crystals are tetragonal, space group P4(1)2(1)2 with unit cell dimensions of a = 28.01, c = 52.95 angstrom. The asymmetric unit consists of one strand of hexanucleotide, one molecule of 4'-epiadriamycin and 34 waters. The R-factor is 20.2% for 1694 reflections with F greater-than-or-equal-to 2-sigma F to 1.7 angstrom. Two asymmetric units associate to generate a duplex complexed with two drug molecules at the d(TpG) steps of the duplex. The chromophore intercalates between these base pairs with the anthracycline amino-sugar positioned in the minor groove. The double helix is a distorted B-DNA type structure. Our structure determination of d(TGATCA) complexed to 4'-epiadriamycin allows for comparison with the previously reported structures of 4'-epiadriamycin bound to d(TGTACA) and to d(CGATCG). The three complexes are similar in gross features and the intercalation geometry is the same irrespective of whether a d(CpG) or d(TpG) sequence is involved. However, the orientation of the amino-sugar displays a dependence on the sequence adjacent to the intercalation site. The flexibility of this amino-sugar may help explain why this class of antibiotics displays a relative insensitivity to base sequence when they bind to DNA.
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页码:3561 / 3566
页数:6
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