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Literature summary extracted from

  • Sen, K.; Hackett, J.C.
    Molecular oxygen activation and proton transfer mechanisms in lanosterol 14alpha-demethylase catalysis (2009), J. Phys. Chem. B, 113, 8170-8182.
    View publication on PubMed

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.14.14.154 Iron
-
 Mycobacterium tuberculosis

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 estriol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis ? + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 estriol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis H37Rv ? + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 lanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis ? + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.154 lanosterol + [reduced NADPH-hemoprotein reductase] + O2
-
 Mycobacterium tuberculosis H37Rv ? + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?

Synonyms

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

General Information

EC Number General Information Comment Organism
1.14.14.154 physiological function two distinct hydrogen-bond networks with the propensity to shuttle protons to the peroxo species in the CYP51 catalytic cycle. The first network is characterized by hydrogen-bonding between the His259, Thr260OH, and distal O2 atom. This hydrogen-bond network can catalyze the formation of compound 0 with a slightly higher barrier and comparable exothermicity to that of the Asp251-H2O-Thr252 shuttle of CYP101. Pursuit of a heterolytic O-O cleavage mechanism for the subsequent formation of compound I is unsuccessful, and exploration of a mechanism initiated by Op-Od bond homolysis realizes an endothermic reaction. Disruption of the His259H+-Thr260OH hydrogen bond followed by the influx of water into the active site and the evolution of an apparent second proton-transfer network, connecting the distal O2 atom to His259H+ and Glu173 via four water molecules. In this configuration of the active site, the peroxo intermediate has an unprecedented triradicaloid electronic structure with either two parallel or antiparallel electrons localized to the FeO2 unit, while a third resides on the protonated Glu173 side chain. This electronic structure is a direct result of the local hydrogen bond and electrostatic environment contributed by the enzyme interior, illustrating an important role for the protein environment to tune the electronic structure of the peroxo intermediate. Protonation of this residue gives rise to a peroxo intermediate with an electronic structure reflecting a potentially less reactive oxyferrous species in the catalytic core Mycobacterium tuberculosis