Azole antifungal drugs have imidazole or triazole rings that coordinate to the heme iron of targeted cytochrome P450 enzymes. The binding of simple imidazoles to crystallographically defined P450 enzymes helps to clarify the parameters that influence binding specificity. This figure shows imidazole bound perpendicular to the heme plane in wild-type P450cam. The paper reports that an L244A mutation in the active site causes an inward shift of Val247 that forces small imidazoles to bind in an orientation roughly parallel rather than perpendicular to the heme plane. This adjustment substantially decreases the affinity of the L244A mutant for imidazole. For further details see Cytochrome P450 active site plasticity: attenuation of imidazole binding in cytochrome P450cam by an L244A mutation by A.Verras et al. (491–496).
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