Amino acid residues in I- and K-helices of rat CYP11B1 and CYP11B2 are important in expression of 18-hydroxylation activity

When a peptide of the 316-398th amino acid residues in CYP11B1 was inserted to the corresponding site in CYP11B2, the 18-hydroxylation activity of the chimera decreased to a level similar to that of CYP11B2. Site-directed mut agenesis studies indicated that this alteration in the activity was due to the change of one amino acid, Ser321-->Pro, which is present at the C-termi nal side of enzyme's I-helix. Conversely, when the corresponding region of CYP11B2 was changed to that of CYP11B1, the 18-hydroxylation activity incre ased to the similar level as that of CYP11B1. This elevation of the activit y seemed to be due to the exchange of two amino acid residues; one, the 321 st residue and the other, the 381st located in the K-helix. The results are discussed in comparison with those obtained by the human isozymes.