Protein Variants | Comment | Organism |
---|---|---|
Gly90Ser | naturally occuring mutation of ERG26 that confers resistance to inhibitor FR171456 | Saccharomyces cerevisiae |
additional information | multiple mutations in ERG26 confer resistance to inhibitor FR171456 in growth and enzyme assays. Some of these ERG26 mutations likely alter Erg26 binding to FR171456, based on a structure model of Erg26 | Saccharomyces cerevisiae |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
FR171456 | a natural specific inhibitor of yeast Erg26p from Monodictys sp.. FR171456 is a natural product with cholesterol-lowering properties in animal models. FR171456 significantly alters the levels of cholesterol pathway intermediates in yeast cells. FR171456 causes significant growth inhibition of strain SC5314 at. Erg26p inhibition requires the 4alpha-carboxyl group of FR171456, substitution of the 4alpha-carboxylic group of FR171456 by a carbobenzylamido group (Compound-1) decreases inhibition | Candida albicans | |
FR171456 | a natural specific inhibitor of mammalian NSDHL from Monodictys sp.. FR171456 is a natural product with cholesterol-lowering properties in animal models. FR171456 significantly alters the levels of cholesterol pathway intermediates in human cells. R171456 inhibits an artificial Hepatitis C viral replicon, and has broad antifungal activity, suggesting potential additional utility as an anti-infective. In a screen to profile compound activity against 503 cancer cell lines only five cell lines are sensitive to FR171456 with IC50 values below 0.005 mM. Calcidiol, a cholesterol metabolite situated downstream of NSDHL, is decreased in a FR171456 dose-dependent manner, consistent with a reduction of cholesterol synthesis, and new derivatives of NSDHL substrates are deteremined in the cells that are no longer effective as substrates | Homo sapiens | |
FR171456 | a natural specific inhibitor of yeast Erg26p from Monodictys sp.. Genomic profiling identifies Erg26p as the FR171456 target, the ERG26 heterozygous strain (erg26DELTA/ERG26) shows the most significant hypersensitivity to FR171456. FR171456 is a natural product with cholesterol-lowering properties in animal models. FR171456 significantly alters the levels of cholesterol pathway intermediates in yeast cells. FR171456 causes significant growth inhibition of strain BY4743 at concentrations up to 0.2 mM. Multiple mutations, e.g. Gly90Ser, in enzyme ERG26 confer resistance to FR171456 in growth and enzyme assays. FR171456 inhibits an artificial Hepatitis C viral replicon, and has broad antifungal activity, suggesting potential additional utility as an anti-infective. Erg26p inhibition requires the 4a-carboxyl group of FR171456, substitution of the 4alpha-carboxylic group of FR171456 by a carbobenzylamido group (Compound-1) decreases inhibition by 300fold. FR171456 docking into a homology model of Erg26p. Modelling FR171456 resistance mutations on Erg26p, overview | Saccharomyces cerevisiae |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | Michaelis-Menten kinetics | Homo sapiens | |
additional information | - |
additional information | Michaelis-Menten kinetics | Saccharomyces cerevisiae | |
0.55 | - |
3beta-hydroxy-cholest-8,24-dien-4alpha-carboxylate | pH 7.5, 30°C | Saccharomyces cerevisiae |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | Homo sapiens | - |
a 3-oxosteroid + CO2 + NAD(P)H | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | Saccharomyces cerevisiae | - |
a 3-oxosteroid + CO2 + NAD(P)H | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | Candida albicans | - |
a 3-oxosteroid + CO2 + NAD(P)H | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | Saccharomyces cerevisiae BY4743 | - |
a 3-oxosteroid + CO2 + NAD(P)H | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Candida albicans | Q5A1B0 | - |
- |
Homo sapiens | Q15738 | - |
- |
Saccharomyces cerevisiae | P53199 | - |
- |
Saccharomyces cerevisiae BY4743 | P53199 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
Huh-7 cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
3beta-hydroxy-cholest-8,24-dien-4alpha-carboxylate + NAD+ | - |
Homo sapiens | 4alpha-methyl-cholest-8,24-dien-3-one + CO2 + NADH | - |
? | |
3beta-hydroxy-cholest-8,24-dien-4alpha-carboxylate + NAD+ | - |
Saccharomyces cerevisiae | 4alpha-methyl-cholest-8,24-dien-3-one + CO2 + NADH | - |
? | |
3beta-hydroxy-cholest-8,24-dien-4alpha-carboxylate + NAD+ | - |
Saccharomyces cerevisiae BY4743 | 4alpha-methyl-cholest-8,24-dien-3-one + CO2 + NADH | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | - |
Homo sapiens | a 3-oxosteroid + CO2 + NAD(P)H | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | - |
Saccharomyces cerevisiae | a 3-oxosteroid + CO2 + NAD(P)H | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | - |
Candida albicans | a 3-oxosteroid + CO2 + NAD(P)H | - |
? | |
a 3beta-hydroxysteroid-4alpha-carboxylate + NAD(P)+ | - |
Saccharomyces cerevisiae BY4743 | a 3-oxosteroid + CO2 + NAD(P)H | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | ERG26p structure homology modeling based on the crystal structure of Pseudomonas aeruginosa UDP-N-acetylglucosamine 4-epimerase complexed with UDP-N-acetylgalactosamine, PDB ID 1SB8 | Saccharomyces cerevisiae |
Synonyms | Comment | Organism |
---|---|---|
Erg26 | - |
Saccharomyces cerevisiae |
Erg26 | - |
Candida albicans |
Erg26p | - |
Saccharomyces cerevisiae |
Erg26p | - |
Candida albicans |
NSDHL | - |
Homo sapiens |
sterol-4-alpha-carboxylate-3-dehydrogenase | - |
Homo sapiens |
sterol-4-alpha-carboxylate-3-dehydrogenase | - |
Saccharomyces cerevisiae |
sterol-4-alpha-carboxylate-3-dehydrogenase | - |
Candida albicans |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
30 | - |
assay at | Homo sapiens |
30 | - |
assay at | Saccharomyces cerevisiae |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
7.5 | - |
assay at | Saccharomyces cerevisiae |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD(P)+ | - |
Candida albicans | |
NAD+ | - |
Homo sapiens | |
NAD+ | - |
Saccharomyces cerevisiae |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00135 | - |
FR171456 | in vitro inhibition, pH 7.5, 30°C | Saccharomyces cerevisiae |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000063 | - |
in a Huh-7 cell-based assay, pH 7.5, 30°C | Homo sapiens | FR171456 | |
0.0022 | - |
in vitro inhibition, pH 7.5, 30°C | Saccharomyces cerevisiae | FR171456 | |
0.036 | - |
in a K-562 cell-based assay, pH 7.5, 30°C | Homo sapiens | FR171456 | |
0.08 | - |
in a Hep-G2 cell-based assay, pH 7.5, 30°C | Homo sapiens | FR171456 |
General Information | Comment | Organism |
---|---|---|
metabolism | the sterol-4-alpha-carboxylate-3-dehydrogenase is an essential enzyme in the ergosterol/cholesterol biosynthesis pathway | Homo sapiens |
metabolism | the sterol-4-alpha-carboxylate-3-dehydrogenase is an essential enzyme in the ergosterol/cholesterol biosynthesis pathway | Saccharomyces cerevisiae |
metabolism | the sterol-4-alpha-carboxylate-3-dehydrogenase is an essential enzyme in the ergosterol/cholesterol biosynthesis pathway | Candida albicans |
additional information | ERG26p structure homology modeling based on the crystal structure of Pseudomonas aeruginosa UDP-N-acetylglucosamine 4-epimerase complexed with UDP-N-acetylgalactosamine, PDB ID 1SB8 | Saccharomyces cerevisiae |
physiological function | the sterol-4-alpha-carboxylate-3-dehydrogenase is an essential enzyme in the ergosterol/cholesterol biosynthesis pathway | Homo sapiens |
physiological function | the sterol-4-alpha-carboxylate-3-dehydrogenase is an essential enzyme in the ergosterol/cholesterol biosynthesis pathway | Saccharomyces cerevisiae |
physiological function | the sterol-4-alpha-carboxylate-3-dehydrogenase is an essential enzyme in the ergosterol/cholesterol biosynthesis pathway | Candida albicans |