CYP1B1- and CYP1A1-Template systems and their application to metabolism and inhibition
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Le résumé fourni par la source
Prediction of cytochrome P450 (CYP)-mediated metabolism is crucial for assessing the safety of chemicals. An in silico system to reproduce CYP1B1-mediated reactions has been developed by the reverse construction of ligand-accessible spaces from ligand assemblies as a fused grid Template* system. There are close similarities between Templates of CYP1B1 and previously established CYP1A1 (Genes & Environ 2023) in the distribution area, Site of oxidation, and the available Width, except for the use of Position 52’ (Pier-sitting) and the lack of use of the bottom in the middle region (Rings F and Ea) on CYP1B1-Template. Experiments using various substrates of both enzymes further suggested the distinct localization of Bay-2 residues on Templates of CYP1A1 and CYP1B1. More than 260 reactions of CYP1A1/1B1 ligands were examined on the present CYP1A1- and CYP1B1-Template systems. From their placements on the Templates and rules for interaction modes, verifications of good and poor substrates, regio/stereo-selectivity, and inhibition became faithfully available for these ligands. To understand the structural basis of the inhibitory interaction, various inhibitors were applied to the Templates and verified modes of the steric interactions. Both the hangings at Position 32 of CYP1A1 ligands and the adherence at Positions 24–52 of CYP1B1 ligands are suggested to retard the dissociation of Bay-2 residues from ligand molecules. Dissociation interference of ligands with Bay-2 residue is thus possible to be a mechanism of ligand-mediated inhibition on CYP1A1 and CYP1B1.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- CYP1B1- and CYP1A1-Template systems and their application to metabolism and inhibition
- Date Crossref
- 26/12/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Tohoku University pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Health Sciences Center for Biological Safety and Research pays non établi dans la noticeStructure de recherche
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Nagoya City University pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Occupational Safety and Health pays non établi dans la noticeÉtablissement de santé
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Graduate School of Pharmaceutical Sciences Division of Drug Metabolism and Molecular Toxicology pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Data Science pays non établi dans la noticeUniversité ou école supérieure
Tohoku University, Center for Biological Safety and Research — National Institute of Health Sciences et Nagoya City University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.