Sterol 14-alpha demethylase cyp51A

Function

Sterol 14alpha-demethylase, encoded by cyp51A and cyp51B, that plays a critical role in the third module of ergosterol biosynthesis pathway, being ergosterol the major sterol component in fungal membranes that participates in a variety of functions. The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (By similarity). In filamentous fungi, during the initial step of this module, lanosterol (lanosta-8,24-dien-3beta-ol) can be metabolized to eburicol. Sterol 14alpha-demethylase catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of both these sterols in the form of formate, and converts eburicol and lanosterol to 14-demethyleburicol (4,4,24-trimethylergosta-8,14,24(28)-trienol) and 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, respectively, which are further metabolized by other enzymes in the pathway to ergosterol. Can also use substrates not intrinsic to fungi, such as 24,25-dihydrolanosterol (DHL), producing 4,4'-dimethyl-8,14-cholestadien-3-beta-ol, but at lower rates than the endogenous substrates (By similarity).

Classification

Family (Pfam)

PF00067 p450

InterPro

CYP450_sterol_14alpha_dmase, Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-IV, Cyt_P450_sf

Functional cluster

Oxidoreductases, Catalases & Peroxidases

Gene Ontology · 8

• GO:0005789 endoplasmic reticulum membrane
• GO:0020037 heme binding
• GO:0005506 iron ion binding
• GO:0008168 methyltransferase activity
• GO:0016491 oxidoreductase activity
• GO:0008398 sterol 14-demethylase activity
• GO:0006696 ergosterol biosynthetic process
• GO:0032259 methylation

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Sterol 14-alpha demethylase 0.98
• Sterol 14-alpha demethylase 0.98
• Sterol 14-alpha demethylase rstn2 0.97
• Sterol 14-alpha demethylase resB 0.97
• Sterol 14-alpha demethylase CYP51A 0.97
• Sterol 14-alpha demethylase 0.96
• Sterol 14-alpha demethylase cyp51B 0.96
• Sterol 14-alpha demethylase CYP51A 0.95
• Lanosterol 14-alpha demethylase erg11 0.95
• Eburicol 14-alpha-demethylase 0.94
• Sterol 14-alpha demethylase 0.94
• Lanosterol 14-alpha demethylase CYP51 0.94

Co-cited proteins · studied together in the literature

• Sterol 14-alpha demethylase cyp51B 7 shared papers
• Transcription regulator srbA precursor 2 shared papers
• Delta(24(24(1)))-sterol reductase erg4B 3 shared papers
• ABC multidrug transporter mdr4 2 shared papers
• Major facilitator superfamily multidrug transporter mdr3 1 shared papers
• ABC multidrug transporter E 1 shared papers
• ABC multidrug transporter B 1 shared papers
• Major facilitator superfamily multidrug transporter mfsB 1 shared papers
• Major facilitator superfamily multidrug transporter mfsC 1 shared papers
• ABC multidrug transporter mdr1 2 shared papers
• Major facilitator superfamily transporter mfsA 1 shared papers
• ABC multidrug transporter C 1 shared papers

Literature · 25 cited papers

• In vitro and in vivo efficacy of a novel and long-acting fungicidal azole, PC1244, on Aspergillus fumigatus infection. Antimicrob. Agents Chemother. · 2018
• In Vitro biochemical study of CYP51-mediated azole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. · 2015
• SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus. PLoS Genet. · 2011
• SREBP-dependent triazole susceptibility in Aspergillus fumigatus is mediated through direct transcriptional regulation of erg11A (cyp51A). Antimicrob. Agents Chemother. · 2012
• The structure-function relationship of the Aspergillus fumigatus cyp51A L98H conversion by site-directed mutagenesis: the mechanism of L98H azole resistance. Fungal Genet. Biol. · 2011
• Three-dimensional models of 14alpha-sterol demethylase (Cyp51A) from Aspergillus lentulus and Aspergillus fumigatus: an insight into differences in voriconazole interaction. Int. J. Antimicrob. Agents · 2011
• An improved model of the Aspergillus fumigatus CYP51A protein. Antimicrob. Agents Chemother. · 2011
• SreA-mediated iron regulation in Aspergillus fumigatus. Mol. Microbiol. · 2008
• Ergosterol biosynthesis pathway in Aspergillus fumigatus. Steroids · 2008
• A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob. Agents Chemother. · 2007
• Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole. Curr. Genet. · 2006
• Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature · 2005
• … and 13 more in the literature graph