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Literature summary extracted from

  • McLean, K.J.; Warman, A.J.; Seward, H.E.; Marshall, K.R.; Girvan, H.M.; Cheesman, M.R.; Waterman, M.R.; Munro, A.W.
    Biophysical characterization of the sterol demethylase P450 from Mycobacterium tuberculosis, its cognate ferredoxin, and their interactions (2006), Biochemistry, 45, 8427-8443.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.14.154 gene RV0764c, coexpression with ferredoxin in Escherichia coli strain HMS174 (DE3) Mycobacterium tuberculosis
1.14.15.36 expression in Escherichia coli Mycobacterium tuberculosis

General Stability

EC Number General Stability Organism
1.14.14.154 the P450 form is stabilized by estriol Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.14.154 1-phenylimidazole heme iron-coordinating inhibitor Mycobacterium tuberculosis
1.14.14.154 4-phenylimidazole heme iron-coordinating inhibitor Mycobacterium tuberculosis
1.14.14.154 clotrimazole
-
 Mycobacterium tuberculosis
1.14.14.154 econazole
-
 Mycobacterium tuberculosis
1.14.14.154 fluconazole
-
 Mycobacterium tuberculosis
1.14.14.154 ketoconazole
-
 Mycobacterium tuberculosis
1.14.14.154 miconazole
-
 Mycobacterium tuberculosis

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.14.14.154 additional information
-
 additional information steady-state kinetic and thermodynamic analysis Mycobacterium tuberculosis

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.14.154 Iron cysteinate- and aqua-ligated heme iron, P450 formation involves residue Cys394, Cys 394 thiol is deprotonated to thiolate in the ferric form, and ferredoxin-bound [3Fe-4S] iron-sulfur cluster Mycobacterium tuberculosis
1.14.15.36 Iron
-
 Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.15.36 estriol + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2 Mycobacterium tuberculosis
-
 ? + formate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O
-
 ?
1.14.15.36 estriol + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2 Mycobacterium tuberculosis H37Rv
-
 ? + formate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.154 Mycobacterium tuberculosis
-
 gene RV0764c
-
1.14.15.36 Mycobacterium tuberculosis P9WPP9
-
-
1.14.15.36 Mycobacterium tuberculosis H37Rv P9WPP9
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.14.14.154 recombinant enzyme from Escherichia coli strain HMS174 (DE3) by two different steps of anion exchange chromatography and hydroxyapaptite chromatography to homogeneity Mycobacterium tuberculosis
1.14.15.36 recombinant protein Mycobacterium tuberculosis

Reaction

EC Number Reaction Comment Organism Reaction ID
1.14.14.154 a 14alpha-methylsteroid + 3 [reduced NADPH-hemoprotein reductase] + 3 O2 = a DELTA14-steroid + formate + 3 [oxidized NADPH-hemoprotein reductase] + 4 H2O heme iron reduction as a rate-limiting step Mycobacterium tuberculosis
a

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.14.154 2-phenylimidazole + [reduced NADPH-hemoprotein reductase] + O2 2-phenylimidazole binding causes thermally induced alterations in CYP51 active site structure and/or binding modes for the small ligand Mycobacterium tuberculosis ?
-
 ?
1.14.14.154 estriol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis ?
-
 ?
1.14.14.154 additional information P420 formation process with protonation of Cys394 and structure by binding of CO to P450, overview Mycobacterium tuberculosis ?
-
 ?
1.14.15.36 estriol + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2
-
 Mycobacterium tuberculosis ? + formate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O
-
 ?
1.14.15.36 estriol + 6 reduced ferredoxin [iron-sulfur] cluster + 6 H+ + 3 O2
-
 Mycobacterium tuberculosis H37Rv ? + formate + 6 oxidized ferredoxin [iron-sulfur] cluster + 4 H2O
-
 ?

Subunits

EC Number Subunits Comment Organism
1.14.14.154 additional information detailed spectroscopic structure analysis of enzyme with bound ligands, overview Mycobacterium tuberculosis

Synonyms

EC Number Synonyms Comment Organism
1.14.14.154 CYP51
-
 Mycobacterium tuberculosis
1.14.14.154 additional information the enzyme belongs to the sterol demethylase family Mycobacterium tuberculosis
1.14.14.154 sterol demethylase P450
-
 Mycobacterium tuberculosis
1.14.15.36 CYP51
-
 Mycobacterium tuberculosis
1.14.15.36 sterol demethylase 450
-
 Mycobacterium tuberculosis

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
1.14.14.154 additional information
-
 thermal inactivation kinetics 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 Ferredoxin Fdx binds a [3Fe-4S] iron-sulfur cluster, encoded by gene RV0763c adejacent to the gene encoding the enzyme Mycobacterium tuberculosis
1.14.15.36 Ferredoxin
-
 Mycobacterium tuberculosis
1.14.15.36 heme heme-iron reduction is the rate limiting step in catalysis. Protonation of the cysteinate ligand to the ferrous CYP51 underlies the collapse of the Fe(II)-CO adduct of the enzyme from its P450 to its P420 form. The protonation is reversible and the rate of P420 formation is substantially retarded in the estriol-bound form of CYP51 Mycobacterium tuberculosis