Binding of ATP to human DNA Topoisomerase I resulting in an alteration of conformation of the enzyme

中國醫藥大學機構典藏 China Medical University Repository, Taiwan > 醫學院 > 分子系統生物醫學研究所 > 期刊論文 > Item 310903500/1841

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题名:	Binding of ATP to human DNA Topoisomerase I resulting in an alteration of conformation of the enzyme
作者:	陳慧婕(Hui-Jye Chen);(Jaulang Hwang)
贡献者:	醫學院分子系統生物醫學研究所
关键词:	DNA topoisomerase I;ATP;ATP-inhibitory effect;conformational change;dual functions
日期:	1999-10
上传时间:	2009-08-19 17:09:34 (UTC+8)
摘要:	It has been known for some time that ATP inhibits the DNA relaxation activity of human DNA topoisomerase I. However, the underlying mechanism of this inhibitory effect remains largely unknown. Using filter binding assays, the binding of human DNA topoisomerase I to DNA was decreased in the presence of ATP. This result suggests that the inhibition of DNA relaxation activity of human DNA topoisomerase I by ATP is at the binding step rather than at the nicking or resealing step. DNA topoisomerase I cleavage assay further supports this notion. ATP-agarose binding and UV cross-linking assays also demonstrate that ATP directly and specifically binds human DNA topoisomerase I. To address whether the ATP binding results in conformational changes in human DNA topoisomerase I, various proteases were employed for detecting potential protein conformational changes. Our results indicated that the proteolytic susceptibilities of trypsin and chymotrypsin were altered in the presence of ATP. The result suggests that the conformation of human DNA topoisomerase I was altered upon ATP binding. In addition, the binding between ATP and human DNA topoisomerase I was also reduced by increasing concentrations of DNA. Our data suggests that human DNA topoisomerase I exhibits at least two incompatible conformations. One conformation is in the form of a topoisomerase I–ATP complex, which inhibits DNA relaxation activity of human DNA topoisomerase I, and the other, a topoisomerase I–DNA complex, which exerts DNA relaxation activity. Our studies identify the role of ATP in the regulation of human DNA topoisomerase I and provide a substantial implication of how human DNA topoisomerase I compromises its versatile functions.
關聯:	EUROPEAN JOURNAL OF BIOCHEMISTRY265(1):367~375
显示于类别:	[分子系統生物醫學研究所] 期刊論文

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