Structural characteristics of cytochrome P-450. Possible location of the heme-binding cysteine in determined amino-acid sequences.
Computer-aided analyses were made of the complete amino-acid sequences of two P-450 species, the phenobarbital-inducible major P-450 of rat liver microsomes (P-450PB) and camphor-hydroxylating P-450 of Pseudomonas putida (P-450cam). Statistically significant homology was recognized between the two P-450 sequences, but these sequences were not related to those of other groups of hemoproteins, such as hemoglobins, peroxidases, and cytochrome c's and b's. Two highly homologous regions, HR1 and HR2, and two other weakly homologous regions were found on optimally matched alignment of the P-450 sequences. The secondary structures of the two P-450's predicted by current prediction methods bear strong resemblance at these homologous regions. Both HR1 and HR2 contain a cysteine residue near the center of the homologous regions, and they are the only regions that show significant homology among all 48 combinations of local sequences around the cysteine residues (six on P-450PB and eight on P-450cam). HR1 is located in the N-proximal half of the molecule, is rich in hydrophilic residues, and is predicted to be helical. On the other hand, HR2 is close to the C-terminus, has intermediate hydrophobicity, and may take a complex secondary structure of a turn-sheet-helix. The amino-acid sequences around the HR1 and HR2 regions are also well conserved in another P-450 species, rabbit P-450LM2.
D000595:Amino Acid Sequence; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003545:Cysteine / Q000302:isolation & purification*; D003577:Cytochrome P-450 Enzyme System; D006420:Hemeproteins; D006801:Humans; D010944:Plants; D011487:Protein Conformation; D011549:Pseudomonas; D051381:Rats; D011956:Receptors, Cell Surface / Q000302:isolation & purification*; D013045:Species Specificity; D013329:Structure-Activity Relationship; D013552:Swine
D006420:Hemeproteins; D011956:Receptors, Cell Surface; C028027:heme receptor; D003577:Cytochrome P-450 Enzyme System; D003545:Cysteine