The unique P450 architecture is designed, in part, to enable the structure to adopt open and closed conformations. These changes are required to provide substrate access to the active site. Some of these motions also appear to be important in proton-coupled electron transfer associated with O2 activation. Solvent protons must have access to the active site to properly protonate the iron-linked O2 molecule, so a shift from the totally closed to at least partially open conformations is required. Such dynamics are probably shared by all P450s. Unique to drugmetabolizing P450s is the requirement that the active site adapt to substrates of very different sizes and shapes. Crystal structures, biophysical studies, and molecular dynamics have provided important insights into how drug-etabolizing P450s, especially CYP3A4, structurally adapt to a variety of inhibitors and substrates.
CITATION STYLE
Poulos, T. L. (2014). Cytochrome P450 dynamics. In Fifty Years of Cytochrome P450 Research (pp. 75–94). Springer Japan. https://doi.org/10.1007/978-4-431-54992-5_4
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