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Literature summary extracted from

  • Eddine, A.N.; von Kries, J.P.; Podust, M.V.; Warrier, T.; Kaufmann, S.H.; Podust, L.M.
    X-ray structure of 4,4-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51) (2008), J. Biol. Chem., 283, 15152-15159.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.14.14.154 drug development the enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plants, and development of more potent and selective CYP51 inhibitors is an important biological objective Mycobacterium tuberculosis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.14.14.154 CYP51 in complex with 4,4'-dihydroxybenzophenone, enzyme in 20 mM Tris-HCl, pH 7.5, 200 mM NaCl, and 0.5 mM EDTA, is mixed with 4,4'-dihydroxybenzophenone, which is dissolved in Me2SO at 100 mM stock concentration, to final concentrations of 0.2 mM for protein and ligand resulting in needle-like crystals, larger crystals are obtained by hanging drop vapor diffusion method from 1.2 M lithium sulfate, 0.1 M HEPES, pH 7.5, and 2% isopropyl alcohol, cryoprotection by 20% glycerol, X-ray diffraction structure determination and analysis at 1.95 A resolution Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.14.154 11-ketoestrone type I binding mechanism Mycobacterium tuberculosis
1.14.14.154 2,7-dihydroxy-9-fluorenone type I binding mechanism Mycobacterium tuberculosis
1.14.14.154 4,4'-dihydroxybenzophenone binds at the active site via a type I mechanism targeting the flexible region, binding structure and kinetics, overview Mycobacterium tuberculosis
1.14.14.154 estriol a substrate analogue Mycobacterium tuberculosis
1.14.14.154 fluconazole a clinical drug Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.14.154 Fe2+ a cytochrome P450 enzyme Mycobacterium tuberculosis
1.14.14.154 additional information divalent metal ion is required for the catalytic reaction Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.14.154 24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis
-
 (3beta,5alpha)-4,4-dimethylcholesta-8,14-dien-3-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis H37Rv
-
 (3beta,5alpha)-4,4-dimethylcholesta-8,14-dien-3-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 eburicol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis
-
 ?
-
 ?
1.14.14.154 eburicol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis H37Rv
-
 ?
-
 ?
1.14.14.154 lanosterol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis
-
 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 lanosterol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis H37Rv
-
 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis
-
 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2 Mycobacterium tuberculosis H37Rv
-
 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.154 Mycobacterium tuberculosis P9WPP9
-
-
1.14.14.154 Mycobacterium tuberculosis H37Rv P9WPP9
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.14.154 24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis (3beta,5alpha)-4,4-dimethylcholesta-8,14-dien-3-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis H37Rv (3beta,5alpha)-4,4-dimethylcholesta-8,14-dien-3-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 eburicol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis ?
-
 ?
1.14.14.154 eburicol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis H37Rv ?
-
 ?
1.14.14.154 lanosterol + O2 + NADPH + H+
-
 Mycobacterium tuberculosis 4,4-dimethyl-5alpha-cholesta-8,14,24-triene-3beta-ol + formate + NADP+ + H2O
-
 ?
1.14.14.154 lanosterol + O2 + NADPH + H+
-
 Mycobacterium tuberculosis H37Rv 4,4-dimethyl-5alpha-cholesta-8,14,24-triene-3beta-ol + formate + NADP+ + H2O
-
 ?
1.14.14.154 lanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 lanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis H37Rv 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis H37Rv 4alpha-methyl-5alpha-ergosta-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Subunits

EC Number Subunits Comment Organism
1.14.14.154 More three-dimensional modeling Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
1.14.14.154 CYP51
-
 Mycobacterium tuberculosis
1.14.14.154 sterol 14alpha-demethylase
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.14.14.154 37
-
 assay at Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.14.14.154 7.5
-
 assay at Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.14.154 cytochrome P450 a cytochrome P450 enzyme Mycobacterium tuberculosis