Modelling of three-dimensional structures of cytochromes P450 11B1 and 11B2.
The final steps of the biosynthesis of glucocorticoids and mineralocorticoids in the adrenal cortex require the action of two different cytochromes P450--CYP11B1 and CYP11B2. Homology modelling of the three-dimensional structures of these cytochromes was performed based on crystallographic coordinates of two bacterial P450s, CYP102 (P450BM-3) and CYP108 (P450terp). Principal attention was given to the modelling of the active sites and a comparison of the active site structures of CYP11B1 and CYP11B2 was performed. It can be demonstrated that key residue contacts within the active site appear to depend on the orientation of the heme. The obtained 3D structures of CYP11B1 and CYP11B2 were used for investigation of structure-function relationships of these enzymes. Previously obtained results on naturally occurring mutants and on mutants obtained by site-directed mutagenesis are discussed.
Belkina
N V
NV
Institute of Biomedical Chemistry RAMS, Pogodinskaya str. 10, 119992, Moscow, Russia.
Lisurek
M
M
Ivanov
A S
AS
Bernhardt
R
R
D000595:Amino Acid Sequence; D001665:Binding Sites; D003461:Crystallography; D019405:Cytochrome P-450 CYP11B2 / Q000737:chemistry*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D012984:Software; D013252:Steroid 11-beta-Hydroxylase / Q000737:chemistry*; D013329:Structure-Activity Relationship
D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase