STRUCTURE AND DYNAMICS OF DISTAMYCIN-A WITH D(CGCAAATTGGC)-D(GCCAATTTGCG) AT LOW DRUG-DNA RATIOS

被引:19
作者
PELTON, JG
WEMMER, DE
机构
[1] UNIV CALIF BERKELEY,DEPT CHEM,1 CYCLOTRON RD,BERKELEY,CA 94720
[2] UNIV CALIF BERKELEY LAWRENCE BERKELEY LAB,DIV CHEM BIODYNAM,BERKELEY,CA 94720
关键词
D O I
10.1080/07391102.1990.10507791
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
Two-dimensional NMR has been used to study the interaction of distamycin A with d(CGCAAA- TTGGC):d(GCCAATTTGCG) at low and intermediate drug:DNA ratios (<2.0). Drug- DNA contacts were identified by nuclear Overhauser effect spectroscopy, which also served to monitor exchange of the drug between different binding sites. At low drug:DNA ratios (0.5), distamycin A binds in two orientations within the five central A-T base pairs and has a preference (2.2:1) for binding with the formyl end directed toward the 5′ side of the A-rich strand. The pattern of drug-DNA contacts corresponding to the preferred binding orientation are consistent with the drug sliding between adjacent AAAT and AATT binding sites at a rate that is fast on the NMR time scale. Similarly, the pattern of NOEs associated with the less favored orientation are consistent with the drug sliding between adjacent AATT and ATTT sites, again in fast exchange. Off-rates for the drug from the major and minor binding orientations were measured to be 2.4 ±1.5 and 3.3 ± 1.5 s-1, respectively, at 35°C. At intermediate drug:DNA ratios (1.3) exchange of the drug between the two one-drug and the two sites of a two-drag complex is observed. Off-rates for both drags from the 2:1 complex were measured to be 1.0 ±0.5 s-1(35°C). © Taylor & Francis Group, LLC.
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页码:81 / 97
页数:17
相关论文
共 49 条
[1]   H-1 TWO-DIMENSIONAL NUCLEAR OVERHAUSER EFFECT AND RELAXATION STUDIES OF POLY(DA).POLY(DT) [J].
BEHLING, RW ;
KEARNS, DR .
BIOCHEMISTRY, 1986, 25 (11) :3335-3346
[2]   ENTHALPY ENTROPY COMPENSATIONS IN DRUG DNA-BINDING STUDIES [J].
BRESLAUER, KJ ;
REMETA, DP ;
CHOU, WY ;
FERRANTE, R ;
CURRY, J ;
ZAUNCZKOWSKI, D ;
SNYDER, JG ;
MARKY, LA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (24) :8922-8926
[3]  
CARRONDO MAA, BIOCHEMISTRY-US, V28, P7849
[4]   CONFORMATIONAL STUDIES OF D-(AAAAATTTTT)2 USING CONSTRAINTS FROM NUCLEAR OVERHAUSER EFFECTS AND FROM QUANTITATIVE-ANALYSIS OF THE CROSS-PEAK FINE-STRUCTURES IN TWO-DIMENSIONAL H-1 NUCLEAR MAGNETIC-RESONANCE SPECTRA [J].
CELDA, B ;
WIDMER, H ;
LEUPIN, W ;
CHAZIN, WJ ;
DENNY, WA ;
WUTHRICH, K .
BIOCHEMISTRY, 1989, 28 (04) :1462-1471
[5]   SEQUENCE-SPECIFIC RECOGNITION OF DEOXYRIBONUCLEIC-ACID - CHEMICAL SYNTHESIS AND NUCLEAR MAGNETIC-RESONANCE ASSIGNMENT OF THE IMINO PROTONS OF LAMBDA-OR3 OPERATOR DEOXYRIBONUCLEIC-ACID [J].
CHOU, SH ;
HARE, DR ;
WEMMER, DE ;
REID, BR .
BIOCHEMISTRY, 1983, 22 (13) :3037-3041
[6]   A BIFURCATED HYDROGEN-BONDED CONFORMATION IN THE D(A.T) BASE-PAIRS OF THE DNA DODECAMER D(CGCAAATTTGCG) AND ITS COMPLEX WITH DISTAMYCIN [J].
COLL, M ;
FREDERICK, CA ;
WANG, AHJ ;
RICH, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8385-8389
[7]   MOLECULAR-STRUCTURE OF THE NETROPSIN-D(CGCGATATCGCG) COMPLEX - DNA CONFORMATION IN AN ALTERNATING AT SEGMENT [J].
COLL, M ;
AYMAMI, J ;
VANDERMAREL, GA ;
VANBOOM, JH ;
RICH, A ;
WANG, AHJ .
BIOCHEMISTRY, 1989, 28 (01) :310-320
[8]   PROTON NUCLEAR MAGNETIC-RESONANCE INVESTIGATION OF THE CONFORMATION AND DYNAMICS IN THE SYNTHETIC DEOXYRIBONUCLEIC-ACID DECAMERS D(ATATCGATAT) AND D(ATATGCATAT) [J].
FEIGON, J ;
DENNY, WA ;
LEUPIN, W ;
KEARNS, DR .
BIOCHEMISTRY, 1983, 22 (25) :5930-5942
[9]   DETERMINATION OF EQUILIBRIUM BINDING-AFFINITY OF DISTAMYCIN AND NETROPSIN TO THE SYNTHETIC DEOXYOLIGONUCLEOTIDE SEQUENCE D(GGTATACC)2 BY QUANTITATIVE DNASE-I FOOTPRINTING [J].
FISH, EL ;
LANE, MJ ;
VOURNAKIS, JN .
BIOCHEMISTRY, 1988, 27 (16) :6026-6032
[10]  
Hahn F. E, 1975, ANTIBIOTICS, V3, P79