CYP51—the omnipotent P450

@article{Lepesheva2004CYP51theOP,
  title={CYP51—the omnipotent P450},
  author={Galina I. Lepesheva and Michael R. Waterman},
  journal={Molecular and Cellular Endocrinology},
  year={2004},
  volume={215},
  pages={165-170}
}
The CYPome (Cytochrome P450 complement) of Aspergillus nidulans.
CYP51 from Trypanosoma brucei is obtusifoliol-specific.
New isoforms of CYP51 (sterol 14alpha-demethylase), an essential enzyme in sterol biosynthesis and primary target of azole antimycotic drugs, are found in pathogenic protists, Trypanosoma brucei(TB),
CYP51 from Trypanosoma cruzi
TLDR
The phyla-specific residue can be used to predict preferred substrates of new CYP51 sequences and subsequently for the development of new artificial substrate analogs, which might serve as highly specific inhibitors able to kill human parasites.
Fungal cytochrome P450 sterol 14α-demethylase (CYP51) and azole resistance in plant and human pathogens
TLDR
Although no crystal structure is available yet for any fungal CYP51, homology modeling using structures from other origins as template allowed deducing models for fungal orthologs and served to map amino acid changes known from clinical and field isolates to explain CYP 51-based azole resistance.
Characterization of the cytochrome P450 monooxygenase genes (P450ome) from the carotenogenic yeast Xanthophyllomyces dendrorhous
TLDR
The carotenogenic yeast X. dendrorhous has thirteen P450-encoding genes having potential functions in primary, secondary and xenobiotic metabolism reactions, including some genes of great interest for fatty acid hydroxylation and aromatic compound degradation.
Expression and Homology Modeling of Sterol 14alpha-Demethylase from Magnaporthe Grisea
TLDR
The spectral data showed that diniconazole exhibited a high affinity for MGCYP51, coincided with the implication of molecular docking, which elucidated the reasonability and reliability of the 3D model and docking model, which can be hopefully used to virtually screen the more potent azole fungicides for M GCYP51.
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References

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Sterol 14-demethylase P450 (CYP51) provides a breakthrough for the discussion on the evolution of cytochrome P450 gene superfamily.
TLDR
Molecular phylogenetic analysis demonstrated that CYP51 appeared in the prokaryotic era and distributed into most kingdoms concomitant with phylogenetic divergence, the first evolutionary evidence indicating the proKaryotic origin of P450.
Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species.
TLDR
The results suggest that P45014DM may be an ancient P450 which arose before the divergence of major eukaryotic branches and has been conserved throughout evolution, and the first example of orthologous P450s occurring in distinct kingdoms.
Structural requirements for substrate recognition of Mycobacterium tuberculosis 14 alpha-demethylase: implications for sterol biosynthesis.
TLDR
Substrate binding to MT 14DM seems to share common features with all eukaryotic 14 alpha-demethylases, the MT form seemingly having the broadest substrate recognition of all forms of 14alpha-dem methylase studied so far.
Folding Requirements Are Different between Sterol 14α-Demethylase (CYP51) from Mycobacterium tuberculosis and Human or Fungal Orthologs*
TLDR
Characterization of wild type protein and three mutants, including examination of catalytic activity, secondary and tertiary structure analysis by circular dichroism and tryptophan fluorescence, and studies of both equilibrium and temporal MTCYP51 unfolding behavior, shows that Arg-448 does not play any role in P450 function or maintenance of the native structure.
The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans.
TLDR
While human cytochrome p450 databases have swelled with a flood of new human sequence variants, the functional characterization of the corresponding gene products has not kept pace, so researchers have begun to apply the tools of proteomics as well as homology-based and ab initio modeling to salient questions of cyto chrome p450 structure/function.
The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols.
Sterol biosynthesis requires the removal of the 14 alpha-methyl group from lanosterol in animals and fungi and from obtusifoliol in plants. This reaction is catalyzed by a microsomal cytochrome P450,
The CYP2 family: models, mutants and interactions.
  • D. Lewis
  • Chemistry, Biology
    Xenobiotica; the fate of foreign compounds in biological systems
  • 1998
TLDR
The homology models of CYP2 family enzymes appear to show self-consistency with the currently accumulated information from site-directed mutagenesis and chemical modification of amino acid residues known to affect redox partner interactions.
Cytochrome P450 and the individuality of species.
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  • Biology
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TLDR
The biosynthesis of cholesterol in bacteria is discussed in relation to CYP51 as a lanosterol 14 alpha-demethylase, which may have been the first eukaryotic P450.
Conservation in the CYP51 family. Role of the B' helix/BC loop and helices F and G in enzymatic function.
TLDR
Mutagenesis of corresponding residues in human CYP51 implies that the conserved amino acids might be essential for the evolutionary conservation of sterol 14 alpha-demethylation from bacteria to mammals.
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