ArticleBiochemistry2010
Structures of cytochrome P450 2B4 complexed with the antiplatelet drugs ticlopidine and clopidogrel .
Article in Biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Multiresolution molecular dynamics simulations reveal the interplay between conformational variability and functional interactions in membrane-bound cytochrome P450 2B4.Protein science : a publication of the Protein Society · 2024Article
- Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Four Decades of Cytochrome P450 2B Research: From Protein Adducts to Protein Structures and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Inhibition of CYP2C8 by Acyl Glucuronides of Gemfibrozil and Clopidogrel: Pharmacological Significance, Progress and Challenges.Biomolecules · 2022Review
- CYP2J2 Molecular Recognition: A New Axis for Therapeutic Design.Pharmacology & therapeutics · 2020Review
- So many roads traveled: A career in science and administration.The Journal of biological chemistry · 2020Article
- Use of Phenoxyaniline Analogues To Generate Biochemical Insights into the Interactio n of Polybrominated Diphenyl Ether with CYP2B Enzymes.Biochemistry · 2018Article
- Capturing the photo-signaling state of a photoreceptor in a steady-state fashion by binding a transition metal complex.Protein science : a publication of the Protein Society · 2017Article
- Halogen-π Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.ACS chemical biology · 2017Article
- Effect of detergent binding on cytochrome P450 2B4 structure as analyzed by X-ray crystallography and deuterium-exchange mass spectrometry.Biophysical chemistry · 2016Article
- Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis.Nature communications · 2016Article
- Article
- A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs.International journal of molecular sciences · 2016Article
- 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
- The role of cytochrome P450 2B6 and 2B4 substrate access channel residues predicted based on crystal structures of the amlodipine complexes.Archives of biochemistry and biophysics · 2014Article
- A structural snapshot of CYP2B4 in complex with paroxetine provides insights into ligand binding and clusters of conformational states.The Journal of pharmacology and experimental therapeutics · 2013Article
- Structural diversity of eukaryotic membrane cytochrome p450s.The Journal of biological chemistry · 2013Review
- Article
- Trendspotting in the Protein Data Bank.FEBS letters · 2013Review
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8 authors.
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Abstract
Prior X-ray crystal structures of rabbit cytochrome P450 2B4 (2B4) in complexes with various imidazoles have demonstrated markedly different enzyme conformations depending on the size of the inhibitor occupying the active site. In this study, structures of 2B4 were determined with the antiplatelet drugs clopidogrel and ticlopidine, which were expected to have greater freedom of movement in the binding pocket. Ticlopidine could be modeled into the electron density maps in two distinct orientations, both of which are consistent with metabolic data gathered with other mammalian P450 enzymes. Results of ligand docking and heme-induced NMR relaxation of drug protons showed that ticlopidine was preferentially oriented with the chlorophenyl group closest to the heme. Because of its stereocenter, clopidogrel was easier to fit in the electron density and exhibited a single orientation, which points the chlorophenyl ring toward the heme. The C(α) traces of both complexes aligned very well with each other and revealed a compact, closed structure that resembles the conformation observed in two previously determined 2B4 structures with the small molecule inhibitors 4-(4-chlorophenyl)imidazole and 1-(4-chlorophenyl)imidazole. The 2B4 active site is able to accommodate small ligands by moving only a small number of side chains, suggesting that ligand reorientation is energetically favored over protein conformational changes for binding of these similarly sized molecules. Adjusting both protein conformation and ligand orientation in the active site gives 2B4 the flexibility to bind to the widest range of molecules, while also being energetically favorable.
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