A hypothetical model for the active site of human cytochrome P4502E1

1. A model for the active site structure of human cytochrome P4502E1 based on the coordinates of cytochrome P450BM-3 crystal structure and the sequence analysis information on P4502E1 was proposed. 2. The sequence alignment of mammalian P4502 family and P450BM-3 indicated a 48%, similarity and 25% identity. Secondary structural prediction displayed a similar pattern of distribution in the main frame of secondary elements, alpha-helices and beta-sheets. The locations of secondary elements also mapped well. In addition, the amino acids responsible for the conserved secondary structural regions showed the most similarity between the two proteins. In contrast, the amino acids responsible for the loop region had the least similarity in our alignment. 3. The predicted P4502E1 active site model shows that the active site is small and contains mainly hydrophobic residues. The substrate binding pocket is located on top of pyrrole rings A and D of the haen; in contrast, the access to B and C rings is partially or completely blocked by protein side chains. 4. Residues within possible contact of a representative substrate, N-nitrosodimethylamine, are He115, Ala299, Thr303, Val364 and possibly He469.