PMID: 18186328Jan 12, 2008Paper

Identification of endocrine disruptor biodegradation by integration of structure-activity relationship with pathway analysis

Environmental Science & Technology
Tadashi KadowakiMinoru Kanehisa

Abstract

We present a SAR method that can predict estrogen-like endocrine disrupting chemical (EDC) activity as well as key biodegradation steps for detoxification. This method is based on a recent graph-mining algorithm developed by Kudo et al., which generates a set of descriptors from all potent chemical fragments (including rings). This method is novel in that it achieves chemical diversity in the training data set by sampling another data set of larger diversity. The model achieved an 83% accuracy prediction rate, and identified 1291 EDC candidates from the KEGG database. From this set of candidate compounds, bisphenol A was chosen for assay validation and biodegradation pathway analysis. Results showed that bisphenol A exhibited estrogen-like activity and was degraded in three distinct reactions. The prediction model provided information on the mechanism of the ligand-target binding, such as key functional groups involved. We focused on the enzyme commission number, which is useful for analyses of biodegradation pathways. Results identified oxygenases, ether hydrolases, and carbon-halide lyases as being important in the biodegradation pathway. This combined approach provided new information regarding the biodegradation of EDCs, an...Continue Reading

References

Dec 1, 1992·Journal of Computer-aided Molecular Design·D A Loughney, C F Schwender
Dec 1, 1996·Chemical Research in Toxicology·C L WallerL E Gray
Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·B D GehmJ L Jameson
Jul 17, 1998·Current Opinion in Chemical Biology·L L Wong
Apr 4, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·R M BlairD M Sheehan
Feb 24, 2001·Journal of Chemical Information and Computer Sciences·L M ShiD M Sheehan
Aug 20, 2003·Environmental Toxicology and Chemistry·Joanna S JaworskaPhilip H Howard
Apr 29, 2004·SAR and QSAR in Environmental Research·A H AsikainenK A Tuppurainen
Apr 29, 2004·SAR and QSAR in Environmental Research·A R CunninghamH S Rosenkranz
Jul 28, 2004·Bioscience, Biotechnology, and Biochemistry·Kengo InoueHideaki Nojiri
Jan 7, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shigeyuki KitamuraShigeru Ohta
Feb 22, 2005·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Tetsuya AdachiGozoh Tsujimoto
Dec 31, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sean EkinsTatiana Nikolskaya
Dec 31, 2005·Nucleic Acids Research·Minoru KanehisaMika Hirakawa
May 23, 2007·Journal of Chemical Information and Modeling·Mina OhMinoru Kanehisa

❮ Previous
Next ❯

Citations

Dec 28, 2010·Water Research·Wanpeng LiuJay Gan
Aug 14, 2010·Environmental Science & Technology·Chunying WangLingyan Zhu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioremediation (ASM)

Bioremediation is the treatment and removal of harmful pollutants or contaminants through the use of microorganisms. Discover the latest research here.

Biosynthetic Transformations

Biosyntheic transformtions are multi-step, enzyme-catalyzed processes where substrates are converted into more complex products in living organisms. Simple compounds are modified, converted into other compounds, or joined together to form macromolecules. Discover the latest research on biosynthetic transformations here.