Application | Comment | Organism |
---|---|---|
pharmacology | squalene epoxidase is an attractive potential target for drugs used to inhibit the growth of pathogenic fungi or to lower cholesterol level in humans | Saccharomyces cerevisiae |
Crystallization (Comment) | Organism |
---|---|
analysis of the terbinafine-squalene epoxidase mode of interaction by docking studies followed by molecular dynamics simulations and quantum interaction energy calculations. In the energetically most likely orientation of terbinafine its interaction energy with the protein is ca. 120 kJ/mol. In the favorable position the terbinafine lipophilic moiety is located vertically inside the squalene epoxidase binding pocket with the tert-butyl group oriented toward its center, resulting in squalene epoxidase conformational changes and preventing the natural substrate from being able to bind to the enzyme's active site. Strongest interaction between terbinafine and squalene poxide stems from hydrogen bonding between hydrogen-bond donors, hydroxyl group of Tyr90 and amine nitrogen atom of terbinafine | Saccharomyces cerevisiae |
Protein Variants | Comment | Organism |
---|---|---|
F402L | the point mutation causes terbinafine resistance | Saccharomyces cerevisiae |
F420L | the point mutation causes terbinafine resistance | Saccharomyces cerevisiae |
F430S | the point mutation causes terbinafine resistance | Saccharomyces cerevisiae |
L251F | the point mutation causes terbinafine resistance | Saccharomyces cerevisiae |
additional information | mutations of amino acids belonging to the FAD I fingerprint motif, e.g. Gly27Ser and Gly30Ser, reduce the enzyme in vitro activity | Saccharomyces cerevisiae |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
terbinafine | noncompetitive inhibition, binding structure analysis, strongest interaction between terbinafine and enzyme stems from hydrogen bonding between hydrogen-bond donors, hydroxyl group of Tyr90 and amine nitrogen atom of terbinafine, mechanism of squalene epoxidase inhibition, overview. Inhibitor identification via docking studies followed by molecular dynamics simulations, based on PDB IDS 2QA1 and 1PBE templates, and quantum interaction energy calculations, overview | Saccharomyces cerevisiae |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Saccharomyces cerevisiae | - |
- |
- |
Subunits | Comment | Organism |
---|---|---|
More | the enzyme shows a two-domain structure with the FAD cofactor and the substrate binding domains | Saccharomyces cerevisiae |
Synonyms | Comment | Organism |
---|---|---|
squalene epoxidase | - |
Saccharomyces cerevisiae |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | dependent on, binds at a domain with a Rossmann fold, containing the 25GlyXGlyXXGly30 sequence | Saccharomyces cerevisiae |
General Information | Comment | Organism |
---|---|---|
metabolism | squalene epoxidase is a key FAD-dependent enzyme of ergosterol and cholesterol biosynthetic pathways | Saccharomyces cerevisiae |