Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate
Abstract
:1. Introduction
2. Results
2.1. Surface Plasmon Resonance
2.2. Spectral Titration Analysis
2.3. Enzyme Activity Assay
2.4. Molecular Docking
3. Discussion
4. Materials and Methods
4.1. Samples
4.2. Surface Plasmon Resonance
- (1)
- 1:1 (Langmuir) binding [57]: , where Kd—equilibrium dissociation constant, koff—dissociation rate constant, kon—association rate constant.
- (2)
- Two-state (conformational change) binding [58]: , where Kd—equilibrium dissociation constant, koff1—dissociation rate constant, kon1—association rate constant, kon2—forward rate constant for CP ↔ CP* transition, koff2—backward rate constant for CP ↔ CP* transition.
4.3. Spectral Titration Analysis
4.4. Enzyme Assay
4.5. Molecular Docking
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Compound | kon | koff | Kd, μM | Evaluation Model |
---|---|---|---|---|
lanosterol | kon (1/Ms) = 41.4 ± 5.0 | koff (1/s × 10−4) = 1.0 ± 0.2 | 2.4 | Langmuir 1:1 |
baicalein | kon1 (1/Ms) = 146 ± 20 | koff1 (1/s × 10−4) = 100 ± 20 | 12.5 | Two state reaction |
kon2 (1/s × 10−4) = 27 ± 3 | koff2 (1/s × 10−4) = 6 ± 1 | |||
luteolin | kon1 (1/Ms) = 282 ± 40 | koff1 (1/s × 10−4) = 190 ± 30 | 20.0 | Two state reaction |
kon2 (1/s × 10−4) = 33 ± 4 | koff2 (1/s × 10−4) = 14 ± 2 | |||
luteolin 7,3′-disulfate | kon (1/Ms) = 294.0 ± 32.3 | koff (1/s × 10−4) = 8.4 ± 2.0 | 2.9 | Langmuir 1:1 |
Compound | Relative Activity, % |
---|---|
No compound | 100.0 |
Baicalein (25 μM) | 89.4 |
Luteolin (25 μM) | 92.6 |
Luteolin 7,3′-disulfate (25 μM) | 49.9 |
Ketoconazole (5 μM) | 5.4 |
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Kaluzhskiy, L.; Ershov, P.; Yablokov, E.; Shkel, T.; Grabovec, I.; Mezentsev, Y.; Gnedenko, O.; Usanov, S.; Shabunya, P.; Fatykhava, S.; et al. Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate. Molecules 2021, 26, 2237. https://doi.org/10.3390/molecules26082237
Kaluzhskiy L, Ershov P, Yablokov E, Shkel T, Grabovec I, Mezentsev Y, Gnedenko O, Usanov S, Shabunya P, Fatykhava S, et al. Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate. Molecules. 2021; 26(8):2237. https://doi.org/10.3390/molecules26082237
Chicago/Turabian StyleKaluzhskiy, Leonid, Pavel Ershov, Evgeniy Yablokov, Tatsiana Shkel, Irina Grabovec, Yuri Mezentsev, Oksana Gnedenko, Sergey Usanov, Polina Shabunya, Sviatlana Fatykhava, and et al. 2021. "Human Lanosterol 14-Alpha Demethylase (CYP51A1) Is a Putative Target for Natural Flavonoid Luteolin 7,3′-Disulfate" Molecules 26, no. 8: 2237. https://doi.org/10.3390/molecules26082237