CRYSTAL-STRUCTURE OF D(CGCGAATTCGCG) COMPLEXED WITH PROPAMIDINE, A SHORT-CHAIN HOMOLOG OF THE DRUG PENTAMIDINE

被引:67
作者
NUNN, CM [1 ]
JENKINS, TC [1 ]
NEIDLE, S [1 ]
机构
[1] INST CANC RES,CANC RES CAMPAIGN,BIOMOLEC STRUCT UNIT,SUTTON SM2 5NG,SURREY,ENGLAND
关键词
D O I
10.1021/bi00213a012
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 crystal structure of the complex between propamidine and the self-complementary DNA dodecamer d(CGCGAATTCGCG) duplex has been determined to a resolution of 2.1 angstrom and an R-factor of 17.4%. The propamidine binds to the DNA within the minor groove, with specific hydrogen-bonding interactions from the amidinium groups to the bases and sugar groups of the DNA, via a 4-base-pair binding site. A network of water molecules lies over the mouth of the minor groove. The structure provides a rationale for the superior DNA-binding properties of propamidine as compared to pentamidine [cf. Edwards, K. J., Jenkins, T. C., & Neidle, S. (1992) Biochemistry 31, 7104-7109]. This is seen to result from (i) decreased minor groove width at the binding site and (ii) reduced mobility of the bound propamidine molecule.
引用
收藏
页码:13838 / 13843
页数:6
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