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MetaCyc Enzyme: cytochrome P450 51

Gene: ERG11 Accession Number: YHR007C (MetaCyc)

Synonyms: CYP51

Species: Saccharomyces cerevisiae

Summary:
cytochrome P450 51 is the major cytochrome P450 enzyme in Saccharomyces cerevisiae [Turi92], and the only known P450 enzyme distributed widely in eukaryotes with a conserved metabolic role [Aoyama96]. The enzyme, which is more closely related to mammalian P450s than to the bacterial P450cam, catalyzes the oxidative removal of the 14α-methyl group (C-32) of the sterol lanosterol, which is removed as formate. This is an essential reaction in the biosynthetic pathway for ergosterol [Kalb87], and is thus a useful target for antifungal agents [Venkateswarlu97].

The enzymes has been purified to homogeneity and characterized extensively [Yoshida84]. ERG11 message levels increase during growth on glucose, in the presence of heme, during oxygen limiting growth conditions and during anaerobic growth [Turi92]. A three-dimensional molecular model of the enzyme has been constructed [Lewis99].

Two P450 enzymes are involved in ergosterol biosynthesis in yeast, the other one is C-22 sterol desaturase, encoded by ERG5 [Hata83].

Locations: plasma membrane

Map Position: [120,084 <- 121,676] (21.34 centisomes)

Molecular Weight of Polypeptide: 60.72 kD (from nucleotide sequence), 58.0 kD (experimental) [Yoshida84 ]

Unification Links: DIP:DIP-7886N , Mint:MINT-1325794 , Protein Model Portal:P10614 , SGD:S000001049 , SMR:P10614 , String:4932.YHR007C , UniProt:P10614

Relationship Links: Entrez-Nucleotide:PART-OF:M18109 , InterPro:IN-FAMILY:IPR001128 , InterPro:IN-FAMILY:IPR002403 , InterPro:IN-FAMILY:IPR017972 , Pfam:IN-FAMILY:PF00067 , Prints:IN-FAMILY:PR00385 , Prints:IN-FAMILY:PR00465 , Prosite:IN-FAMILY:PS00086

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005886 - plasma membrane [Venkateswarlu97]

Gene Class: UNCLASSIFIED

Credits:
Created 21-Dec-2004 by Hong E , Saccharomyces Genome Database
Revised 16-Jan-2008 by Caspi R , SRI International


Enzymatic reaction of: lanosterol 14a-demethylase (cytochrome P450 51)

lanosterol + 3 NADPH + 3 oxygen + 2 H+ <=> 14-demethyllanosterol + formate + 3 NADP+ + 4 H2O

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

In Pathways: superpathway of ergosterol biosynthesis I , zymosterol biosynthesis

Inhibitors (Unknown Mechanism): buthiobate [Aoyama83] , ketoconazole [Kalb86]

Kinetic Parameters:

Substrate
Km (μM)
Citations
lanosterol
6.9
[Yoshida84]


References

Aoyama83: Aoyama Y, Yoshida Y, Hata S, Nishino T, Katsuki H (1983). "Buthiobate: a potent inhibitor for yeast cytochrome P-450 catalyzing 14 alpha-demethylation of lanosterol." Biochem Biophys Res Commun 115(2);642-7. PMID: 6414474

Aoyama96: Aoyama Y, Noshiro M, Gotoh O, Imaoka S, Funae Y, Kurosawa N, Horiuchi T, Yoshida Y (1996). "Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species." J Biochem (Tokyo) 119(5);926-33. PMID: 8797093

Hata83: Hata S, Nishino T, Katsuki H, Aoyama Y, Yoshida Y (1983). "Two species of cytochrome P-450 involved in ergosterol biosynthesis of yeast." Biochem Biophys Res Commun 116(1);162-6. PMID: 6357195

Kalb86: Kalb VF, Loper JC, Dey CR, Woods CW, Sutter TR (1986). "Isolation of a cytochrome P-450 structural gene from Saccharomyces cerevisiae." Gene 45(3);237-45. PMID: 3542713

Kalb87: Kalb VF, Woods CW, Turi TG, Dey CR, Sutter TR, Loper JC (1987). "Primary structure of the P450 lanosterol demethylase gene from Saccharomyces cerevisiae." DNA 6(6);529-37. PMID: 3322742

Lewis99: Lewis DF, Wiseman A, Tarbit MH (1999). "Molecular modelling of lanosterol 14 alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform: quantitative structure-activity relationships (QSARs) within two related series of antifungal azole derivatives." J Enzyme Inhib 14(3);175-92. PMID: 10445042

Turi92: Turi TG, Loper JC (1992). "Multiple regulatory elements control expression of the gene encoding the Saccharomyces cerevisiae cytochrome P450, lanosterol 14 alpha-demethylase (ERG11)." J Biol Chem 267(3);2046-56. PMID: 1730736

Venkateswarlu97: Venkateswarlu K, Kelly DE, Kelly SL (1997). "Characterization of Saccharomyces cerevisiae CYP51 and a CYP51 fusion protein with NADPH cytochrome P-450 oxidoreductase expressed in Escherichia coli." Antimicrob Agents Chemother 41(4);776-80. PMID: 9087488

Yoshida84: Yoshida Y, Aoyama Y (1984). "Yeast cytochrome P-450 catalyzing lanosterol 14 alpha-demethylation. I. Purification and spectral properties." J Biol Chem 259(3);1655-60. PMID: 6363414


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sun Nov 23, 2014, BIOCYC14B.