2xfh
Structure of cytochrome P450 EryK cocrystallized with inhibitor clotrimazole.Structure of cytochrome P450 EryK cocrystallized with inhibitor clotrimazole.
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEryK is a bacterial cytochrome P450 that catalyzes the last hydroxylation occurring during the biosynthetic pathway of erythromycin A in Streptomyces erythraeus. We report the crystal structures of EryK in complex with two widely used azole inhibitors: ketoconazole and clotrimazole. Both these ligands use their imidazole moiety to coordinate the heme iron of P450s. Nevertheless, because of the different chemical and structural properties of their N1-substituent group, ketoconazole and clotrimazole trap EryK, respectively, in a closed and in an open conformation that resemble the two structures previously described for the ligand-free EryK. Indeed ligands induce a distortion of the internal helix I that affects the accessibility of the binding pocket by regulating the kink of the external helix G via a network of interactions that involves helix F. The data presented thus constitute an example of how a cytochrome P450 may be selectively trapped in different conformational states by inhibitors. Azole drugs trap cytochrome P450 EryK in alternative conformational states.,Montemiglio LC, Gianni S, Vallone B, Savino C Biochemistry. 2010 Sep 16. PMID:20845962[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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