Figure 4
From: Novel insights into P450 BM3 interactions with FDA-approved antifungal azole drugs
Crystal structures of the BM3 heme domain A82F/F87V mutants in complex with different azole drugs. Panel a shows an overlay of various azole-complexed A82F/F87V (DM) BM3 heme domain structures, revealing that a similar overall conformation (“open”, in blue) is adopted by the majority of the monomers. In contrast, a single monomer in the fluconazole complex is in a “closed” stated (shown in green). Panels b-f depict the environment of the bound ligands (clotrimazole - b, tioconazole - c, voriconazole - d and fluconazole - e/f, respectively), with key residues shown in atom colored sticks (ligand with yellow carbons, protein with light blue carbons and heme with purple carbons). Panels g-k depict the corresponding omit electron density (contoured at 3 sigma) for each of the ligands (clotrimazole - g, tioconazole - h, voriconazole - i and fluconazole - j/k) as a blue mesh. With the exception of fluconazole, the conformation of the ligand is similar in the various monomers in the asymmetric unit, and in each instance monomer A is shown. In the case of the fluconazole ligand, both of the conformations observed are depicted in panels e (“open” conformation) and f (“closed” conformation), with the corresponding electron density shown in panels j and k. MPD: 2-methyl-2,4-pentanediol, EDO: 1,2-ethanediol.
