Acidic phospholipids directly inhibit DNA binding of mammalian DNA topoisomerase I

FEBS Letters

Ikegami, Yoji¹  Andoh, Toshiwo¹  Ono, Katsuhiro¹  Tamura, Hiro-omi¹  Sekimizu, Kazuhisa² 

[1] Department of Hygienic Chemistry, Meiji College of Pharmacy, Tanashi-shi, Tokyo 188 Japan;Faculty of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

关键词: Topoisomerase I;    Phospholipid;    CL;    cardiolipin;    PS;    phosphatidylserine;    PI;    phosphatidylinositol;    PG;    phosphatidylglycerol;    PE;    phosphatidylethanolamine;    CPT;    camptothecin;   

DOI  :  10.1016/0014-5793(90)80658-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Inhibition of mammalian DNA topoisomerase I by phospholipids was investigated using purified enzyme. Acidic phospholipids inhibited the DNA relaxation activity of topoisomerase I whereas neutral phospholipid, phosphatidylethanolamine, did not. Accumulation of a protein-DNA cleavable complex, an intermediate which is known to accumulate upon inhibition by a specific inhibitor camptothecin, did not occur. The filter binding assay revealed that the DNA binding activity of the enzyme was inhibited by acidic phospholipids. Moreoever, direct binding of phosphatidylglycerol to topoisomerase I was demonstrated. These results indicated that the inhibitory effect of acidic phospholipids on topoisomerase I was due to the loss of the DNA binding of the enzyme as a result of direct interaction between phospholipids and the enzyme.

【 授权许可】

Unknown