An unexpected insight into P450 dynamics
came from the S. solfataricus CYPl 19 structure^^,
the first known thermal stable P450^^. The
structure was solved in two crystal forms: one
with imidazole and one with phenylimidazole
coordinated to the heme iron. Compared to the
phenylimidazole complex, in the imidazole complex,
the C-terminal end of the F helix unwinds
which increases the length of the F/G loop thus
allowing the loop to dip down into the active and
interact with imidazole ligand (Figure 3.20). In
effect, the protein shapes itself around the ligand.
Conformational adaptations also contribute to
the capacity of mammalian drug and xenobiotic
metabolizing enzymes to recognize structurally
diverse substrates. Rabbit microsomal CYP2C5,
a drug and steroid metabolizing enzyme,