Conformational preferences of DNA following damage by aristolochic acids: Structural and energetic insights into the different mutagenic potential of the ALI and ALII-N(6)-dA adducts

Biochemistry
Preetleen KathuriaStacey D Wetmore

Abstract

Aristolochic acids (AAI and AAII), produced by the Aristolochiaceae family of plants, are classified as group I (human) carcinogens by the International Agency for Research on Cancer. These acids are metabolized in cells to yield aristolactams (ALI and ALII, respectively), which further form bulky adducts with the purine nucleobases. Specifically, the adenine lesions are more persistent in cells and have been associated with chronic renal diseases and related carcinogenesis. To understand the structural basis of the nephrotoxicity induced by AAs, the ALI-N(6)-dA and ALII-N(6)-dA lesions are systematically studied using computational methods. Density functional theory calculations indicate that the aristolactam moiety intrinsically prefers a planar conformation with respect to adenine. Nucleoside and nucleotide models suggest that the anti and syn orientations about the glycosidic bond are isoenergetic for both adducts. Molecular dynamics simulations and free energy calculations reveal that the anti base-displaced intercalated conformation is the most stable conformer for both types of AL-N(6)-dA adducted DNA, which agrees with previous experimental work on the ALII-N(6)-dA adduct and thereby validates our approach. Interestingl...Continue Reading

References

Apr 27, 1999·Journal of Biomolecular Structure & Dynamics·T E CheathamP A Kollman
Jun 3, 1999·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·J P CosynsC van Ypersele de Strihou
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Feb 3, 2005·Environmental and Molecular Mutagenesis·William M BairdBrinda Mahadevan
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Feb 7, 2006·Journal of Molecular Graphics & Modelling·Junmei WangDavid A Case
Mar 30, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Shinya ShibutaniArthur P Grollman
Jul 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Arthur P GrollmanBojan Jelaković
Sep 21, 2007·Nature·Jung-Hyun Min, Nikola P Pavletich
Oct 27, 2007·Trends in Biochemical Sciences·Olivier MaillardHanspeter Naegeli
Dec 7, 2007·Chemical Research in Toxicology·Suse BroydeDinshaw J Patel
Dec 12, 2007·Journal of Computational Chemistry·Ross C WalkerDavid A Case
Jul 3, 2008·The Journal of Physical Chemistry. B·In Suk Joung, Thomas E Cheatham
Nov 22, 2008·Nature Reviews. Molecular Cell Biology·Philip C Hanawalt, Graciela Spivak
Feb 11, 2010·Physical Chemistry Chemical Physics : PCCP·Agnes NoyModesto Orozco

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Citations

Apr 23, 2016·Physical Chemistry Chemical Physics : PCCP·N R JenaP C Mishra
Dec 12, 2017·Clinical Kidney Journal·Benjamin A VervaetAnja Verhulst
Jul 6, 2021·Archives of Toxicology·Jingjing WanYang Luan

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