Sterol 14alpha-demethylase Cytochrome P450 (CYP51), a P450 in All Biological Kingdoms

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2006 Sep 12

PMID 16963187

Citations 179

Authors

Galina I Lepesheva

Michael R Waterman

Affiliations

Soon will be listed here.

Abstract

The CYP51 family is an intriguing subject for fundamental P450 structure/function studies and is also an important clinical drug target. This review updates information on the variety of the CYP51 family members, including their physiological roles, natural substrates and substrate preferences, and catalytic properties in vitro. We present experimental support for the notion that specific conserved regions in the P450 sequences represent a CYP51 signature. Two possible roles of CYP51 in P450 evolution are discussed and the major approaches for CYP51 inhibition are summarized.

Citing Articles

Antioxidant potential, antimicrobial activity, polyphenol profile analysis, and cytotoxicity against breast cancer cell lines of hydro-ethanolic extracts of leaves of ( L.) from Eastern Morocco.

Tikent A, Laaraj S, Bouddine T, Chebaibi M, Bouhrim M, Elfazazi K Front Chem. 2024; 12:1505473.

PMID: 39665002 PMC: 11631630. DOI: 10.3389/fchem.2024.1505473.

Strain Expressed Constitutively High Levels of Sterol 14-α Demethylase mRNA, While Transporter and mRNA Expression Was Induced After Addition of Short Chain Azoles.

Berstecher N, Burmester A, Gregersen D, Tittelbach J, Wiegand C J Fungi (Basel). 2024; 10(11).

PMID: 39590650 PMC: 11595479. DOI: 10.3390/jof10110731.

Comprehensive Review on Plant Cytochrome P450 Evolution: Copy Number, Diversity, and Motif Analysis From Chlorophyta to Dicotyledoneae.

Fang Y, Tai Z, Hu K, Luo L, Yang S, Liu M Genome Biol Evol. 2024; 16(11).

PMID: 39506518 PMC: 11586672. DOI: 10.1093/gbe/evae240.

Azole Combinations and Multi-Targeting Drugs That Synergistically Inhibit .

Toepfer S, Keniya M, Lackner M, Monk B J Fungi (Basel). 2024; 10(10).

PMID: 39452650 PMC: 11508803. DOI: 10.3390/jof10100698.

Exploring the Antibiofilm Effect of Sertraline in Synergy with Essential Oil to Counteract Species.

Barbarossa A, Rosato A, Carrieri A, Fumarola L, Tardugno R, Corbo F Pharmaceuticals (Basel). 2024; 17(9).

PMID: 39338275 PMC: 11435152. DOI: 10.3390/ph17091109.

References

Urbina J, Payares G, Molina J, Sanoja C, Liendo A, Lazardi K . Cure of short- and long-term experimental Chagas' disease using D0870. Science. 1996; 273(5277):969-71. DOI: 10.1126/science.273.5277.969. View

Rozman D, Stromstedt M, Waterman M . The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family. Arch Biochem Biophys. 1996; 333(2):466-74. DOI: 10.1006/abbi.1996.0416. View

Kahn R, Bak S, Olsen C, Svendsen I, Moller B . Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14alpha-demethylase from Sorghum bicolor (L.) Moench. J Biol Chem. 1996; 271(51):32944-50. DOI: 10.1074/jbc.271.51.32944. View

Kelly S, Lamb D, Baldwin B, Corran A, Kelly D . Characterization of Saccharomyces cerevisiae CYP61, sterol delta22-desaturase, and inhibition by azole antifungal agents. J Biol Chem. 1997; 272(15):9986-8. DOI: 10.1074/jbc.272.15.9986. View

Yoshida Y, Noshiro M, Aoyama Y, Kawamoto T, Horiuchi T, Gotoh O . Structural and evolutionary studies on sterol 14-demethylase P450 (CYP51), the most conserved P450 monooxygenase: II. Evolutionary analysis of protein and gene structures. J Biochem. 1998; 122(6):1122-8. DOI: 10.1093/oxfordjournals.jbchem.a021870. View

Stromstedt M, Waterman M, Haugen T, Tasken K, Parvinen M, Rozman D . Elevated expression of lanosterol 14alpha-demethylase (CYP51) and the synthesis of oocyte meiosis-activating sterols in postmeiotic germ cells of male rats. Endocrinology. 1998; 139(5):2314-21. DOI: 10.1210/endo.139.5.5984. View

Vidakovic M, Sligar S, Li H, Poulos T . Understanding the role of the essential Asp251 in cytochrome p450cam using site-directed mutagenesis, crystallography, and kinetic solvent isotope effect. Biochemistry. 1998; 37(26):9211-9. DOI: 10.1021/bi980189f. View

Aoyama Y, Horiuchi T, Gotoh O, Noshiro M, Yoshida Y . CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51. J Biochem. 1998; 124(4):694-6. DOI: 10.1093/oxfordjournals.jbchem.a022167. View

Lamb D, Kelly D, Manning N, Hollomon D, Kelly S . Expression, purification, reconstitution and inhibition of Ustilago maydis sterol 14 alpha-demethylase (CYP51; P450(14DM)). FEMS Microbiol Lett. 1998; 169(2):369-73. DOI: 10.1111/j.1574-6968.1998.tb13342.x. View

10.

Asai K, Tsuchimori N, OKONOGI K, Perfect J, Gotoh O, Yoshida Y . Formation of azole-resistant Candida albicans by mutation of sterol 14-demethylase P450. Antimicrob Agents Chemother. 1999; 43(5):1163-9. PMC: 89127. DOI: 10.1128/AAC.43.5.1163. View

11.

Frye L, Leonard D . Lanosterol analogs: dual-action inhibitors of cholesterol biosynthesis. Crit Rev Biochem Mol Biol. 1999; 34(2):123-40. DOI: 10.1080/10409239991209246. View

12.

Cabello-Hurtado F, Taton M, Forthoffer N, Kahn R, Bak S, Rahier A . Optimized expression and catalytic properties of a wheat obtusifoliol 14alpha-demethylase (CYP51) expressed in yeast. Complementation of erg11Delta yeast mutants by plant CYP51. Eur J Biochem. 1999; 262(2):435-46. DOI: 10.1046/j.1432-1327.1999.00376.x. View

13.

Bellamine A, Mangla A, Nes W, Waterman M . Characterization and catalytic properties of the sterol 14alpha-demethylase from Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 1999; 96(16):8937-42. PMC: 17711. DOI: 10.1073/pnas.96.16.8937. View

14.

Nelson D . Cytochrome P450 and the individuality of species. Arch Biochem Biophys. 1999; 369(1):1-10. DOI: 10.1006/abbi.1999.1352. View

15.

Aoyama Y . Recent progress in the CYP51 research focusing on its unique evolutionary and functional characteristics as a diversozyme P450. Front Biosci. 2005; 10:1546-57. DOI: 10.2741/1639. View

16.

Wyand R, Brown J . Sequence variation in the CYP51 gene of Blumeria graminis associated with resistance to sterol demethylase inhibiting fungicides. Fungal Genet Biol. 2005; 42(8):726-35. DOI: 10.1016/j.fgb.2005.04.007. View

17.

El-Sayed N, Myler P, Blandin G, Berriman M, Crabtree J, Aggarwal G . Comparative genomics of trypanosomatid parasitic protozoa. Science. 2005; 309(5733):404-9. DOI: 10.1126/science.1112181. View

18.

Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu D . The genome of the African trypanosome Trypanosoma brucei. Science. 2005; 309(5733):416-22. DOI: 10.1126/science.1112642. View

19.

Kim H, Schaller H, Goh C, Kwon M, Choe S, An C . Arabidopsis cyp51 mutant shows postembryonic seedling lethality associated with lack of membrane integrity. Plant Physiol. 2005; 138(4):2033-47. PMC: 1183393. DOI: 10.1104/pp.105.061598. View

20.

Hankins E, Gillespie J, Aikenhead K, Buckner F . Upregulation of sterol C14-demethylase expression in Trypanosoma cruzi treated with sterol biosynthesis inhibitors. Mol Biochem Parasitol. 2005; 144(1):68-75. DOI: 10.1016/j.molbiopara.2005.08.002. View