Recombinant Human Lanosterol 14-alpha demethylase (CYP51A1)
Description
Biological Function
CYP51A1 performs three sequential oxidations to convert lanosterol or 24,25-dihydrolanosterol into 4,4-dimethylcholesta-8,14,24-trien-3β-ol, a cholesterol precursor . This enzymatic activity:
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Maintains cellular cholesterol homeostasis.
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Modulates meiosis-activating sterols in reproductive tissues .
Research Applications
The recombinant protein is widely used in:
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Drug Discovery: Screening inhibitors like azoles (e.g., ketoconazole) and flavonoids (e.g., luteolin 7,3’-disulfate) .
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Enzyme Kinetics: Studying substrate specificity and catalytic mechanisms .
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Cancer Research: Investigating roles in pancreatic ductal adenocarcinoma (PDAC) cell survival under acidic conditions .
Inhibitor Studies
Luteolin 7,3’-disulfate, a water-soluble flavonoid, inhibits CYP51A1 by binding to substrate access channels or redox partner interfaces . Comparative efficacy:
| Inhibitor | IC₅₀/Effect at 25 μM | Mechanism |
|---|---|---|
| Ketoconazole | 94.6% inhibition | Heme iron coordination |
| Luteolin 7,3’-disulfate | 50.1% inhibition | Access channel blockade |
Role in Cancer
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CYP51A1 overexpression in PDAC cells confers resistance to pH-dependent cell death via SREBF2-mediated regulation .
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Knockdown of CYP51A1 enhances JTC801-induced tumor suppression in xenograft models .
Genetic Variants
Rare missense mutations (e.g., D152G, R277L) disrupt interactions with redox partners or substrates, linked to developmental disorders and azole susceptibility .
Clinical Relevance
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Antifungal Targets: CYP51A1 homologs in fungi are inhibited by azoles, guiding antifungal drug design .
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Cancer Therapeutics: Pharmacological inhibition of CYP51A1 sensitizes PDAC tumors to JTC801, a pH-dependent cytotoxic agent .
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Genetic Diagnostics: Damaging CYP51A1 variants are proposed biomarkers for pediatric cataracts and metabolic disorders .
Product Specs
Note: We prioritize shipping the format currently in stock. If you require a specific format, please specify this in your order notes, and we will accommodate your request to the best of our ability.
Note: All proteins are shipped with standard blue ice packs. Dry ice shipping requires advance notice and incurs additional charges.
The tag type will be determined during production. If you require a specific tag, please inform us, and we will prioritize its development.
Target Background
Recombinant Human Lanosterol 14-alpha demethylase (CYP51A1) is a cytochrome P450 monooxygenase crucial for sterol biosynthesis. Its primary function is the 14-alpha demethylation of lanosterol and 24,25-dihydrolanosterol. This process involves sequential oxidation of the 14-alpha methyl group to a hydroxymethyl group, then a carboxylaldehyde. Subsequently, a delta 14,15 double bond forms in the sterol core, releasing formic acid. Mechanistically, CYP51A1 utilizes molecular oxygen, incorporating one oxygen atom into the substrate and reducing the other to water. The two electrons necessary for this reaction are provided by NADPH via cytochrome P450 reductase (CPR).
- Regulation of human CYP51A1 expression. PMID: 28830911
- Insights into substrate profile, catalytic efficiency, and inhibition susceptibility of human CYP51. PMID: 27313059
- Roles of GDF9 and FSH in regulating cholesterol biosynthesis and CYP51A1 expression in granulosa cells. PMID: 24711211
- Interaction of FoxO4, SREBP2, and HIF2alpha in modulating CYP51 promoter activity. PMID: 24353279
- Link between CYP51A1 and pregnancy pathologies. PMID: 24358204
- Selective interaction of azoles with human cytochrome P450 51A1, with ketoconazole showing highest affinity. PMID: 24502137
- Low nucleotide variability of CYP51A1 in cholesterol and bile acid synthesis and xenobiotic metabolism pathways. PMID: 24362992
- Analysis of the effect of CYP51A1 inhibitor LEK-935 on the proteome of primary human hepatocytes. PMID: 22180046
- Structural similarity of CPY51 across various eukaryotic organisms. PMID: 20547249
- Conformational changes in CYP51 upon ligand binding. PMID: 20149798
- Role of a cAMP-responsive element binding site in sterol regulation of the human lanosterol 14alpha-demethylase gene. PMID: 12145339
- Factors determining the strength of interactions with azoles. PMID: 15611056
- Liver X receptor alpha silencing of CYP51A1 and squalene synthase. PMID: 18676367
