Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DME1664)
DME Name Cytochrome P450 monooxygenase 51A (cyp51A), Aspergillus fumigatus
Synonyms Sterol 14-alpha demethylase; Ergosterol biosynthesis protein cyp51A; AFUA_4G06890; cyp51A; erg11A
Gene Name cyp51A
UniProt ID
CP51A_ASPFU
Gene ID
3509526
EC Number    EC: 1.14.14.154     (Click to Show/Hide the Complete EC Tree)
Oxidoreductase
Oxygen paired donor oxidoreductase
Flavin/flavoprotein donor oxidoreductase
EC: 1.14.14.154
Lineage    Species: Aspergillus fumigatus     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Fungi
Phylum: Ascomycota
Class: Eurotiomycetes
Order: Eurotiales
Family: Aspergillaceae
Genus: Aspergillus
Species: Aspergillus fumigatus
Interactome
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       Interactions between Xenobiotics and DME (XEOTIC)                      
Jump to Detailed Interactome Data                      
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Tissue Distribution Primarily distributed in human lung.
Sequence
MVPMLWLTAYMAVAVLTAILLNVVYQLFFRLWNRTEPPMVFHWVPYLGSTISYGIDPYKF
FFACREKYGDIFTFILLGQKTTVYLGVQGNEFILNGKLKDVNAEEVYSPLTTPVFGSDVV
YDCPNSKLMEQKKFIKYGLTQSALESHVPLIEKEVLDYLRDSPNFQGSSGRVDISAAMAE
ITIFTAARALQGQEVRSKLTAEFADLYHDLDKGFTPINFMLPWAPLPHNKKRDAAHARMR
SIYVDIITQRRLDGEKDSQKSDMIWNLMNCTYKNGQQVPDKEIAHMMITLLMAGQHSSSS
ISAWIMLRLASQPKVLEELYQEQLANLGPAGPDGSLPPLQYKDLDKLPFHQHVIRETLRI
HSSIHSIMRKVKSPLPVPGTPYMIPPGRVLLASPGVTALSDEHFPNAGCWDPHRWENQAT
KEQENDKVVDYGYGAVSKGTSSPYLPFGAGRHRCIGEKFAYVNLGVILATIVRHLRLFNV
DGKKGVPETDYSSLFSGPMKPSIIGWEKRSKNTSK
Pathway Biosynthesis of secondary metabolites (afm01110 )
Metabolic pathways (afm01100 )
Steroid biosynthesis (afm00100 )
Function This enzyme is involved in the biosynthesis of ergosterol, and as a cytochrome P-450 (heme-thiolate) protein acts on a range of steroids with a 14alpha-methyl group, such as obtusifoliol and lanosterol. And it catalyses a hydroxylation and a reduction of the 14alpha-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          1 Drugs
Naproxen
 Drug Info Approved Rheumatoid arthritis ICD11: FA20 [1]
      Preclinical/investigative Agents Click to Show/Hide the Full List of Drugs:          3 Drugs
Obtusifoldienol
 Drug Info Investigative Discovery agent ICD: N.A. [2], [3]
Dihydrolanosterol
 Drug Info Investigative Discovery agent ICD: N.A. [2], [3]
Lanosterol
 Drug Info Investigative Alzheimer disease ICD11: 8A20 [2], [3]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR012865 Nicotinamide (NAM) Nicotinic acid Unclear - Unclear D-ribosylnicotinate [4]
MR004867 5-methoxysalicylic acid Catechol Multi-steps Reaction - Demethylation; Reduction Naproxen [1]
MR004869 5-methoxysalicylic acid Gentistic acid Multi-steps Reaction - Demethylation; Reduction Naproxen [1]
MR012927 Obtusifoldienol Obtusifoldienol Metabolite C1 Oxidation - 14alpha-demethylation Obtusifoldienol [5]
References
1 Utilization of naproxen by Amycolatopsis sp. Poz 14 and detection of the enzymes involved in the degradation metabolic pathway
2 The fungal CYP51s: their functions, structures, related drug resistance, and inhibitors. Front Microbiol. 2019 Apr 24;10:691.
3 Lung colonization by Aspergillus fumigatus is controlled by ZNF77. Nat Commun. 2018 Sep 20;9(1):3835.
4 Nicotinamide riboside and nicotinic acid riboside salvage in fungi and mammals. Quantitative basis for Urh1 and purine nucleoside phosphorylase function in NAD+ metabolism
5 Azole Antifungal Sensitivity of Sterol 14-Demethylase (CYP51) and CYP5218 from Malassezia globosa

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