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Literature summary for 1.14.14.154 extracted from

  • Lepesheva, G.I.; Zaitseva, N.G.; Nes, W.D.; Zhou, W.; Arase, M.; Liu, J.; Hill, G.C.; Waterman, M.R.
    CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B helix defines substrate preferences of sterol 14alpha-demethylase (2006), J. Biol. Chem., 281, 3577-3585.
    View publication on PubMed
Search for more literature for 1.14.14.154

Application

Application Comment Organism
medicine the enzyme is a potential drug target for treatment of Chagas disease Trypanosoma cruzi

Cloned(Commentary)

Cloned (Comment) Organism
gene CYP51, DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic analysis, expression of His-tagged enzyme in Escherichia coli Trypanosoma cruzi

Protein Variants

Protein Variants Comment Organism
I105F sited-directed mutagenesis, exchange of the animal/fungi-like I105 B' helix residue for the F105 found in this position in all plant and the other six CYP51 sequences from Trypanosomatidae dramatically alters the mutant substrate specificity, activity with C4-methylsterol substrate is 3.5fold reduced and activity with norlanosterol and obtusifoliol is increased 150fold and 60fold, respectively, overview Trypanosoma cruzi

Inhibitors

Inhibitors Comment Organism Structure
14alpha-aminomethyl-lanosterol derivatives competitive Trypanosoma cruzi
fluconazole and analogues Trypanosoma cruzi
additional information inhibition kinetics and mechanism Trypanosoma cruzi

Localization

Localization Comment Organism GeneOntology No. Textmining
membrane
-
 Trypanosoma cruzi 16020
-

Metals/Ions

Metals/Ions Comment Organism Structure
Iron a heme iron, DELTA7–8 double bond location is more favorable for coordination of the amino nitrogen to the heme iron Trypanosoma cruzi

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2 Trypanosoma cruzi
-
 ?
-
 ?
24-methylenedihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2 Trypanosoma cruzi
-
 ?
-
 ?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2 Trypanosoma cruzi
-
 ?
-
 ?
norlanosterol + [reduced NADPH-hemoprotein reductase] + O2 Trypanosoma cruzi i.e. 4alpha,4alpha-dimethylcholesta-8,24-dien-3beta-ol ?
-
 ?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2 Trypanosoma cruzi preferred substrate 4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Organism

Organism UniProt Comment Textmining
Trypanosoma cruzi Q7Z1V1 gene CYP51
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography, and anion and cation exchange chromatography Trypanosoma cruzi

Reaction

Reaction Comment Organism Reaction ID
a 14alpha-methylsteroid + 3 [reduced NADPH-hemoprotein reductase] + 3 O2 = a DELTA14-steroid + formate + 3 [oxidized NADPH-hemoprotein reductase] + 4 H2O reaction mechanism, phyla-specific residues in CYP51 Trypanosoma cruzi
a

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
-
 substrate specificities of recombinant wild-type and mutant I105F enzymes, overview Trypanosoma cruzi

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Trypanosoma cruzi ?
-
 ?
24-methylenedihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Trypanosoma cruzi ?
-
 ?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Trypanosoma cruzi ?
-
 ?
additional information substrate specificity, the Trypanosoma cruzi enzyme prefers C4-dimethylsterols substrates, overview Trypanosoma cruzi ?
-
 ?
norlanosterol + [reduced NADPH-hemoprotein reductase] + O2 i.e. 4alpha,4alpha-dimethylcholesta-8,24-dien-3beta-ol Trypanosoma cruzi ?
-
 ?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2 preferred substrate Trypanosoma cruzi 4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Synonyms

Synonyms Comment Organism
CYP51
-
 Trypanosoma cruzi
sterol 14alpha-demethylase
-
 Trypanosoma cruzi