Petasiphenol: A DNA Polymerase Inhibitor
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- 作者：Yoshiyuki Mizushina ; Shinji Kamisuki ; Nobuyuki Kasai ; Tomomi Ishidoh ; Noriko Shimazaki ; Masaharu Takemura ; Hitomi Asahara ; Stuart Linn ; Shonen Yoshida ; Osamu Koiwai ; Fumio Sugawara ; Hiromi Yoshida ; an
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：December 10, 2002
- 年：2002
- 卷：41
- 期：49
- 页码：14463 - 14471
- 全文大小：405K
- 年卷期：v.41,no.49(December 10, 2002)
- ISSN：1520-4995
文摘
Petasiphenol, a bio-antimutagen isolated from a Japanese vegetable, Petasites japonicus,selectively inhibits the activities of mammalian DNA polymerase 
(pol ) in vitro. The compound didnot influence the activities of replicative DNA polymerases such as 
, 
, and 
but also showed no effecteven on the pol 
activity, the three-dimensional structure of which is thought to be highly similar to pol. The inhibitory effect of petasiphenol on intact pol including the BRCA1 C-terminus (BRCT) domainwas dose-dependent, and 50% inhibition was observed at a concentration of 7.8 
M. The petasiphenol-induced inhibition of the pol activity was noncompetitive with respect to both the DNA template-primer and the dNTP substrate. Petasiphenol did not only inhibit the activity of the truncated pol includingthe pol -like core, in which the BRCT motif was deleted in its N-terminal region. BIAcore analysisdemonstrated that petasiphenol bound selectively to the N-terminal domain of pol but did not bind tothe C-terminal region. On the basis of these results, the pol inhibitory mechanism of petasiphenol isdiscussed.
(pol ) in vitro. The compound didnot influence the activities of replicative DNA polymerases such as , , and but also showed no effecteven on the pol activity, the three-dimensional structure of which is thought to be highly similar to pol. The inhibitory effect of petasiphenol on intact pol including the BRCA1 C-terminus (BRCT) domainwas dose-dependent, and 50% inhibition was observed at a concentration of 7.8 M. The petasiphenol-induced inhibition of the pol activity was noncompetitive with respect to both the DNA template-primer and the dNTP substrate. Petasiphenol did not only inhibit the activity of the truncated pol includingthe pol -like core, in which the BRCT motif was deleted in its N-terminal region. BIAcore analysisdemonstrated that petasiphenol bound selectively to the N-terminal domain of pol but did not bind tothe C-terminal region. On the basis of these results, the pol inhibitory mechanism of petasiphenol isdiscussed.