INHIBITION OF ESCHERICHIA-COLI DNA TOPOISOMERASE-I ACTIVITY BY PHOSPHOLIPIDS

被引:43
作者
MIZUSHIMA, T [1 ]
NATORI, S [1 ]
SEKIMIZU, K [1 ]
机构
[1] UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,TOKYO 113,JAPAN
关键词
D O I
10.1042/bj2850503
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 DNA relaxation activity of Escherichia coli DNA topoisomerase I in vitro was greatly inhibited by cardiolipin. Inhibition also occurred to some extent with phosphatidylglycerol from egg yolk. Analysis with synthetic phospholipid revealed that phosphatidylglycerol containing unsaturated fatty acids exhibited a strong inhibitory effect, whereas inhibition by phosphatidylglycerol containing saturated fatty acids was weak. Phosphatidylethanolamine showed no inhibitory effect. Chlorpromazine, which interacts with phospholipids, suppressed the inhibitory effect of cardiolipin. Cardiolipin and phosphatidylglycerol with unsaturated fatty acid precipitated topoisomerase I even at low concentrations, whereas phosphatidylglycerol from egg yolk and a synthetic phosphatidylglycerol containing saturated fatty acids precipitated this enzyme only at high concentrations. One-third of the total topoisomerase I in E. coli was found in the membrane fraction. Treatment of E. coli cells with chlorpromazine resulted in relaxation of plasmid DNA. This DNA relaxation was not observed in a top A mutant, suggesting that this relaxation by chlorpromazine in vivo is catalysed by topoisomerase I.
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页码:503 / 506
页数:4
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