Crystal structure of a thermophilic cytochrome P450 from the archaeon Sulfolobus solfataricus

The structure of the first P450 identified in Archaea, CYP119 from Sulfolob us solfataricus, has been solved in two different crystal forms that differ by the ligand (imidazole or 4-phenylimidazole) coordinated to the heme iro n. A comparison of the two structures reveals an unprecedented rearrangemen t of the active site to adapt to the different size and shape of ligands bo und to the heme iron. These changes involve unraveling of the F helix C-ter minal segment to extend a loop structure connecting the F and G helices, al lowing the longer loop to dip down into the active site and interact with t he smaller imidazole ligand, A comparison of CYP119 with P450cam and P450er yF indicates an extensive clustering of aromatic residues may provide the s tructural basis for the enhanced thermal stability of CYP119. An additional feature of the 4-phenylimidazole-bound structure is a zinc ion tetrahedral ly bound by symmetry-related His and Glu residues.