Crystal structure of a thermophilic cytochrome P450 from the archaeon Sulfolobus solfataricus.
The structure of the first P450 identified in Archaea, CYP119 from Sulfolobus solfataricus, has been solved in two different crystal forms that differ by the ligand (imidazole or 4-phenylimidazole) coordinated to the heme iron. A comparison of the two structures reveals an unprecedented rearrangement of the active site to adapt to the different size and shape of ligands bound to the heme iron. These changes involve unraveling of the F helix C-terminal segment to extend a loop structure connecting the F and G helices, allowing the longer loop to dip down into the active site and interact with the smaller imidazole ligand. A comparison of CYP119 with P450cam and P450eryF indicates an extensive clustering of aromatic residues may provide the structural basis for the enhanced thermal stability of CYP119. An additional feature of the 4-phenylimidazole-bound structure is a zinc ion tetrahedrally bound by symmetry-related His and Glu residues.
Yano
J K
JK
Department of Molecular Biology and Biochemistry and Program in Macromolecular Structure, University of California, Irvine, California 92697-3900, USA.
Koo
L S
LS
Schuller
D J
DJ
Li
H
H
Ortiz de Montellano
P R
PR
Poulos
T L
TL
D019843:Archaeal Proteins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D004583:Electrons; D004926:Escherichia coli / Q000378:metabolism; D005973:Glutamine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D007477:Ions; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D010105:Oxygenases / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012492:Salts / Q000737:chemistry; D013237:Stereoisomerism; D016944:Sulfolobus / Q000201:enzymology*; D013696:Temperature; D013912:Threonine / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
D019843:Archaeal Proteins; D007093:Imidazoles; D007477:Ions; D008024:Ligands; D012492:Salts; D005973:Glutamine; D013912:Threonine; D006639:Histidine; C033023:4(5)-phenylimidazole; C029899:imidazole; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C408874:CYP119 protein, Sulfolobus solfataricus; D015032:Zinc