A Structural Snapshot of CYP2B4 in Complex with Paroxetine Provides Insights into Ligand Binding and Clusters of Conformational States

摘要: 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 A resolution. The revealed a conformation intermediate to that recently amlodipine and more compact 4-(4-chlorophenyl)imidazole terms placement F-G cassette. Moreover, comparison new 15 previously structures some insights into determinants active-site size shape. 2B4-paroxetine is nearly superimposable on closed ligand-free state. Despite overall conformational similarity among multiple structures, cavity volume enlarged. Further analysis accessible space binding pocket near heme reveals subchamber resulted from movement secondary structural elements rearrangements side chains. Overall, results all 16 demonstrate cluster protein conformations were observed presence or absence various ligands.