TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organ...TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organisms were curated from UniProt functional annotation. A unique feature of TSdb is that all the substrates are mapped to identifiers from the KEGG Ligand com- pound database. Thus, TSdb links current metabolic pathway schema with compound transporter systems via the shared compounds in the pathways. Furthermore, all the transporter substrates in TSdb are classified according to their biochemical properties, biological roles and subcellular localizations. In addition to the functional annotation of transporters, extensive compound annotation that includes inhibitor information from the KEGG Ligand and BRENDA databases has been integrated, making TSdb a useful source for the discovery of potential inhibitory mechanisms linking transporter substrates and metabolic enzymes. User-friendly web interfaces are designed for easy access, query and download of the data. Text and BLAST searches against all transporters in the database are provided. We will regularly update the substrate data with evidence from new publications.展开更多
Alternative brominated flame retardants（BFRs） have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers（PBDEs）. For risk assessment of these alternatives, knowledge of the...Alternative brominated flame retardants（BFRs） have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers（PBDEs）. For risk assessment of these alternatives, knowledge of their metabolism via cytochrome P450 enzymes is needed.We have previously proved that density functional theory（DFT） is able to predict the metabolism of PBDEs by revealing the molecular mechanisms. In the current study, the reactivity of 1,2-bis（2,4,6-tribromophenoxy）ethane and structurally similar chemicals with the Compound I model representing the active site of P450 enzymes was investigated. The DFT calculations delineated reaction pathways which lead to reasonable explanations for products that were detected by wet experiments, meanwhile intermediates which cannot be determined were also proposed. Results showed that alkyl hydrogen abstraction will lead to bis（2,4,6-tribromophenoxy）ethanol, which may undergo hydrolysis yielding2,4,6-tribromophenol, a neurotoxic compound. In addition, a general pattern of oxidation reactivity regarding the 2,4,6-tribromophenyl moiety was observed among several model compounds. Our study has provided insights for convenient evaluation of the metabolism of other structurally similar BFRs.展开更多
基金supported by the National High Technology Research and Development Program of China (Grant Nos. 2006AA02Z334, 2006AA02Z314, 2006AA02A312 and 2007AA02Z165)the National Basic Research Program of China (Grant Nos. 2006CB910404 and 2007CB946904)support of the K. C. Wong Education Foundation, Hong Kong
文摘TSdb (http://tsdb.cbi.pku.edu.cn) is the first manually curated central repository that stores formatted information on the substrates of transporters. In total, 37608 transporters with 15075 substrates from 884 organisms were curated from UniProt functional annotation. A unique feature of TSdb is that all the substrates are mapped to identifiers from the KEGG Ligand com- pound database. Thus, TSdb links current metabolic pathway schema with compound transporter systems via the shared compounds in the pathways. Furthermore, all the transporter substrates in TSdb are classified according to their biochemical properties, biological roles and subcellular localizations. In addition to the functional annotation of transporters, extensive compound annotation that includes inhibitor information from the KEGG Ligand and BRENDA databases has been integrated, making TSdb a useful source for the discovery of potential inhibitory mechanisms linking transporter substrates and metabolic enzymes. User-friendly web interfaces are designed for easy access, query and download of the data. Text and BLAST searches against all transporters in the database are provided. We will regularly update the substrate data with evidence from new publications.
基金supported by the National Basic Research Program(No.2013CB430403)the National Natural Science Foundation(Nos.21137001,21325729,and 21173211)of Chinasupported by Supercomputing Center of Dalian University of Technology
文摘Alternative brominated flame retardants（BFRs） have become prevalent as a consequence of restrictions on the use of polybrominated diphenyl ethers（PBDEs）. For risk assessment of these alternatives, knowledge of their metabolism via cytochrome P450 enzymes is needed.We have previously proved that density functional theory（DFT） is able to predict the metabolism of PBDEs by revealing the molecular mechanisms. In the current study, the reactivity of 1,2-bis（2,4,6-tribromophenoxy）ethane and structurally similar chemicals with the Compound I model representing the active site of P450 enzymes was investigated. The DFT calculations delineated reaction pathways which lead to reasonable explanations for products that were detected by wet experiments, meanwhile intermediates which cannot be determined were also proposed. Results showed that alkyl hydrogen abstraction will lead to bis（2,4,6-tribromophenoxy）ethanol, which may undergo hydrolysis yielding2,4,6-tribromophenol, a neurotoxic compound. In addition, a general pattern of oxidation reactivity regarding the 2,4,6-tribromophenyl moiety was observed among several model compounds. Our study has provided insights for convenient evaluation of the metabolism of other structurally similar BFRs.
