Beta-sitosterol-3-O-beta-D-glucopyranoside: a eukaryotic DNA polymerase lambda inhibitor

The Journal of Steroid Biochemistry and Molecular Biology
Y MizushinaHiromi Yoshida

Abstract

Beta-sitosterol-3-O-beta-D-glucopyranoside (compound 1), a steroidal glycoside isolated from onion (Allium cepa L.) selectively inhibited the activity of mammalian DNA polymerase lambda (pol lambda) in vitro. The compound did not influence the activities of replicative DNA polymerases such as alpha, delta and epsilon, but also showed no effect even on the activity of pol beta which is thought to have a very similar three-dimensional structure to the pol beta-like region of pol lambda. Since parts of compound 1 such as beta-sitosterol (compound 2) and D-glucose (compound 3) did not influence the activities of any enzymes tested, the converted structure of compounds 2 and 3 might be important for pol lambda inhibition. The inhibitory effect of compound 1 on both intact pol lambda (i.e. residues 1-575) and a truncated pol lambda lacking the N-terminal BRCA1 C-terminus (BRCT) domain (133-575, del-1 pol lambda) was dose-dependent, and 50% inhibition was observed at a concentration of 9.1 and 5.4 microM, respectively. The compound 1-induced inhibition of del-1 pol lambda activity was non-competitive with respect to both the DNA template-primer and the dNTP substrate. On the basis of these results, the pol lambda inhibitory mechanism ...Continue Reading

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Citations

Oct 29, 2010·Inflammopharmacology·Yuk-Shing ChanShun-Wan Chan
Jul 24, 2008·Public Health Nutrition·Luisa Torres-SanchezLizbeth Lopez-Carrillo
Nov 23, 2007·Natural Product Reports·James R Hanson
Jun 19, 2007·Nutrition and Cancer·Naoki MaedaYoshiyuki Mizushina
Jun 9, 2009·Bioscience, Biotechnology, and Biochemistry·Yoshiyuki Mizushina
Apr 8, 2015·Pharmaceutical Biology·Chawki BensouiciZahia Kabouche
Apr 23, 2013·Journal of Ethnopharmacology·Youn-Hwan HwangJin Yeul Ma
Jun 24, 2014·Journal of Ethnopharmacology·Jinlian ZhaoVéronique Seidel
Jan 24, 2007·Biochemical and Biophysical Research Communications·Chisato IshimaruYoshiyuki Mizushina
Jan 25, 2018·Natural Product Research·Quang Ton ThatPoul Erik Hansen
Apr 9, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sook Wah TangAbdul Manaf Ali
Sep 27, 2019·Natural Product Research·Muhammad Sulaiman ZubairSyariful Anam

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