Molecule Information

General Information of the Molecule (ID: Mol01087)

• Name: Sterol 14-alpha demethylase (CYP51C) ,Aspergillus flavus
• Synonyms: Cytochrome P450 monooxygenase 51C; Ergosterol biosynthesis protein cyp51C; AFLA_100590
• Molecule Type: Protein
• Gene Name: cyp51c
• Sequence:
  MSWPRIGAYALLAFVAIMALNVTYQFLFRMLNKTRPPLVFHWIPFIGSTIHYGMDPYGFF
  FSCREKYGDIFTFILLGRPTTVYLGTQGNEFILNGKLKDVNAEEVYSPLTTPVFGSDVVY
  DCPNSKLIEQKKFIKFGLSQAALEAHVPLIEKEVEDYLAMSPNFHGTSGEVDIPAAMAEI
  TIFTAGSALQGEEVRSKLTTEFAVLYHDLDKGFTPINFMLPWAPLPHNKKRDAAHARMRS
  IYIDIINKRRNAGDNVPEKLDMIGNLMQCTYKNGQPLPDKEIAHIMITLLMAGQHSSSSI
  SSWIMLRLASQPAVVEELYQEQLANLERTGPNGSLAPLQYKDFDNLPLHQNVIRETLRLH
  SSIHSLLRKVKNPLPVPGTPYVIPTSHVLLAAPGVTALSDEYFPNAMAWDPHRWETQAPQ
  ENNKDDIVDYGYGAMSKGTSSPYLPFGAGRHRCIGEKFAYLNLAVIVATMVRHLRFSNLD
  GQTGVPDTDYSSLFSGPMKPARIRWERRAAKSG
• Function: Cytochrome P450 monooxygenase involved in the biosynthesis of ergosterol. The existence of several duplicated sterol 14-alpha demethylase genes could be a good strategy to modulate the composition and fluidity of the cell membrane. Catalyzes C14-demethylation of erburicol to produce 4,4,24-trimethyl cholesta-8,24(28)-dien-3-beta-ol. As a target of azole drugs, plays a crucial role in azole drug susceptibility.
• Uniprot ID: CP51C_ASPFN

Kingdom: Fungi
Phylum: Ascomycota
Class: Eurotiomycetes
Order: Eurotiales
Family: Aspergillaceae
Genus: Aspergillus
Species: Aspergillus flavus

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Voriconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Aspergillus flavus infection [1]

• Resistant Disease: Aspergillus flavus infection [ICD-11: 1F20.1]
• Resistant Drug: Voriconazole
• Molecule Alteration: Missense mutation; p.Y319H
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Aspergillus flavus strain; 5059
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: A novel Y319H substitution in CYP51C associated with azole resistance in Aspergillus flavus.

Disease Class: Invasive aspergillosis [2]

• Resistant Disease: Invasive aspergillosis [ICD-11: 1F20.6]
• Resistant Drug: Voriconazole
• Molecule Alteration: Missense mutation; p.T788G
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Aspergillus flavus strain; 5059
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The T788G mutation in the cyp51C gene confers voriconazole resistance in aspergillus flavus causing aspergillosis.

References

• Ref 1: A Novel Y319H Substitution in CYP51C Associated with Azole Resistance in Aspergillus flavus. Antimicrob Agents Chemother. 2015 Oct;59(10):6615-9. doi: 10.1128/AAC.00637-15. Epub 2015 Jul 27.
• Ref 2: The T788G mutation in the cyp51C gene confers voriconazole resistance in Aspergillus flavus causing aspergillosis. Antimicrob Agents Chemother. 2012 May;56(5):2598-603. doi: 10.1128/AAC.05477-11. Epub 2012 Feb 6.