Molecule Information

General Information of the Molecule (ID: Mol04414)

• Name: Lanosterol 14-alpha demethylase (CYP51A1) ,Homo sapiens
• Synonyms: CYPLI; Cytochrome P450 51A1; Cytochrome P450-14DM; Cytochrome P450LI; Sterol 14-alpha demethylase
• Molecule Type: Protein
• Gene Name: CYP51A1
• Gene ID: 1595
• Sequence:
  MAAAAGMLLLGLLQAGGSVLGQAMEKVTGGNLLSMLLIACAFTLSLVYLIRLAAGHLVQL
  PAGVKSPPYIFSPIPFLGHAIAFGKSPIEFLENAYEKYGPVFSFTMVGKTFTYLLGSDA
  A ALLFNSKNEDLNAEDVYSRLTTPVFGKGVAYDVPNPVFLEQKKMLKSGLNIAHFKQHV
  SI IEKETKEYFESWGESGEKNVFEALSELIILTASHCLHGKEIRSQLNEKVAQLYADLD
  GGF SHAAWLLPGWLPLPSFRRRDRAHREIKDIFYKAIQKRRQSQEKIDDILQTLLDATY
  KDGR PLTDDEVAGMLIGLLLAGQHTSSTTSAWMGFFLARDKTLQKKCYLEQKTVCGENL
  PPLTY DQLKDLNLLDRCIKETLRLRPPIMIMMRMARTPQTVAGYTIPPGHQVCVSPTVN
  QRLKDS WVERLDFNPDRYLQDNPASGEKFAYVPFGAGRHRCIGENFAYVQIKTIWSTML
  RLYEFDL IDGYFPTVNYTTMIHTPENPVIRYKRRSK
• Function: Sterol 14alpha-demethylase that plays a critical role in thecholesterol biosynthesis pathway, being cholesterol the major sterolcomponent in mammalian membranes as well as a precursor for bile acidand steroid hormone synthesis . Cytochrome P450 monooxygenase that catalyzes thethree-step oxidative removal of the 14alpha-methyl group ofsterols such as lanosterol and 24,25-dihydrolanosterol in the form of formate, and converts thesterols to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol and 4,4-dimethyl-8,14-cholestadien-3beta-ol, respectively, which areintermediates of cholesterol biosynthesis . Can also demethylate substrates notintrinsic to mammals, such as eburicol , but at a lower rate than DHL .{ECO:0000269|PubMed:20149798, ECO:0000269|PubMed:8619637,ECO:0000269|PubMed:9559662}.
• Uniprot ID: CP51A_HUMAN
• Ensembl ID: ENSG0000000163018
• HGNC ID: HGNC:2649

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

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) 5 drug(s) in total

Fluconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Fluconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Itraconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Itraconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Ketoconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Ketoconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Posaconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Posaconazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Voriconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Voriconazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

References

• Ref 1: Elucidating the augmented resistance profile of Scedosporium/Lomentospora species to azoles in a cystic fibrosis mimic environment. J Antimicrob Chemother. 2025 Jan 3;80(1):106-115.