ArticleThe Journal of pharmacology and experimental therapeutics2013
A structural snapshot of CYP2B4 in complex with paroxetine provides insights into ligand binding and clusters of conformational states.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Global transcriptome modulation by xenobiotics: the role of alternative splicing in adaptive responses to chemical exposures.Human genomics · 2024Article
- Advancing insights on β-cyclodextrin inclusion complexes with SSRIs through lens of X-ray diffraction and DFT calculation.International journal of pharmaceutics · 2021Article
- Paroxetine-Overview of the Molecular Mechanisms of Action.International journal of molecular sciences · 2021Review
- Interaction of drugs amlodipine and paroxetine with the metabolizing enzyme CYP2B4: a molecular dynamics simulation study.Journal of molecular modeling · 2018Article
- Effect of detergent binding on cytochrome P450 2B4 structure as analyzed by X-ray crystallography and deuterium-exchange mass spectrometry.Biophysical chemistry · 2016Article
- Article
- Structure-Function Analysis of Mammalian CYP2B Enzymes Using 7-Substituted Coumarin Derivatives as Probes: Utility of Crystal Structures and Molecular Modeling in Understanding Xenobiotic Metabolism.Molecular pharmacology · 2016Article
- Functional importance of a peripheral pocket in mammalian cytochrome P450 2B enzymes.Archives of biochemistry and biophysics · 2015Article
- Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography.The Journal of biological chemistry · 2015Article
- Structural and biophysical characterization of human cytochromes P450 2B6 and 2A6 bound to volatile hydrocarbons: analysis and comparison.Molecular pharmacology · 2015Article
- Insights into the role of substrates on the interaction between cytochrome b5 and cytochrome P450 2B4 by NMR.Scientific reports · 2015Article
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Authors and funding
6 authors.
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Abstract
An X-ray crystal structure of CYP2B4 in complex with the drug paroxetine [(3S,4R)-3-[(2H-1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine] was solved at 2.14 Å resolution. The structure revealed a conformation intermediate to that of the recently solved complex with amlodipine and that of the more compact complex with 4-(4-chlorophenyl)imidazole in terms of the placement of the F-G cassette. Moreover, comparison of the new structure with 15 previously solved structures of CYP2B4 revealed some new insights into the determinants of active-site size and shape. The 2B4-paroxetine structure is nearly superimposable on a previously solved closed structure in a ligand-free state. Despite the overall conformational similarity among multiple closed structures, the active-site cavity volume of the paroxetine complex is enlarged. Further analysis of the accessible space and binding pocket near the heme reveals a new subchamber that resulted from the movement of secondary structural elements and rearrangements of active-site side chains. Overall, the results from the comparison of all 16 structures of CYP2B4 demonstrate a cluster of protein conformations that were observed in the presence or absence of various ligands.
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