Yuri Aoyama

Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, 192-8577, Japan

FIGURES

'Figure 1. Sterol biosynthetic pathways of eukaryotes. The red circles indicate the 14-methyl group removed by CYP51. The local structures characteristic for the natural substrates of animal, plant, and fungal 14-demethylation steps are marked by green circles.

Figure 2. CYP51-mediated sterol 14-demethylation reaction consisting of three successive monooxygenations and the active oxygen species responsible to each monooxygenation step. The first and the second steps are ordinary monooxygenation driven by single oxygen activated at the heme iron. However, the last step is driven by the attack of peroxide on the heme iron. C-C bond fission is achieved by cleavage of peroxide linkage of the intermediate as shown in the box.

Figure 3. The relationship between the highly conserved region of CYP51s and SRSs of P450. All known amino acid sequences of eukaryotic CYP51s are aligned. The degree of sequence conservation at each alignment position was calculated as described previously (20). The regions denoted as SRSs 1 through 6 are corresponding to the putative substrate-recognition sites proposed by Goto (20). This figure was modified from that in Ref. 21

Figure 4. Fluconazole resistant CYP51 variants occurring in C. albicans strain DUMC136. Panel A: An amino acid sequence alignment of C. albicans CYP51 variants relating to fluconazole resistance. ATCC-1 and ATCC-2 are the allelic variants of CYP51 occurring in the fluconazole sensitive wild-type C. albicans ATCC 90028. DUMC is the fluconazole-resistant CYP51 variant emerged in the fluconazole resistant strain C. albicans DUMC136. Panel B: The inhibitory effects of fluconazole on lanosterol 14-demethylase activity of three CYP51 variants (35).

Figure 5. Amino acid sequences of the I-helix part of CYP51s from various origins. Note that a triplet "HTS" or "HSS" at the center of I-helix is conserved among all known CYP51s.