The enzyme participates in the biosynthesis of several important sterols such as ergosterol and cholesterol. It is part of a three enzyme system that removes methyl groups from the C-4 position of steroid molecules. The first enzyme, EC 1.14.18.9, 4alpha-methylsterol monooxygenase, catalyses three successive oxidations of the methyl group, resulting in a carboxyl group; the second enzyme, EC 1.1.1.170, catalyses an oxidative decarboxylation that results in a reduction of the 3beta-hydroxy group at the C-3 carbon to an oxo group; and the last enzyme, EC 1.1.1.270, 3beta-hydroxysteroid 3-dehydrogenase, reduces the 3-oxo group back to a 3beta-hydroxyl. If a second methyl group remains at the C-4 position, this enzyme also catalyses its epimerization from 4beta to 4alpha orientation, so it could serve as a substrate for a second round of demethylation. cf. EC 1.1.1.418, plant 3beta-hydroxysteroid-4alpha-carboxylate 3-dehydrogenase (decarboxylating).
The enzyme participates in the biosynthesis of several important sterols such as ergosterol and cholesterol. It is part of a three enzyme system that removes methyl groups from the C-4 position of steroid molecules. The first enzyme, EC 1.14.18.9, 4alpha-methylsterol monooxygenase, catalyses three successive oxidations of the methyl group, resulting in a carboxyl group; the second enzyme, EC 1.1.1.170, catalyses an oxidative decarboxylation that results in a reduction of the 3beta-hydroxy group at the C-3 carbon to an oxo group; and the last enzyme, EC 1.1.1.270, 3beta-hydroxysteroid 3-dehydrogenase, reduces the 3-oxo group back to a 3beta-hydroxyl. If a second methyl group remains at the C-4 position, this enzyme also catalyses its epimerization from 4beta to 4alpha orientation, so it could serve as a substrate for a second round of demethylation. cf. EC 1.1.1.418, plant 3beta-hydroxysteroid-4alpha-carboxylate 3-dehydrogenase (decarboxylating).
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
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
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
Analysis of hedgehog signaling in cerebellar granule cell precursors in a conditional Nsdhl allele demonstrates an essential role for cholesterol in postnatal CNS development.
Significant contributions of the extraembryonic membranes and maternal genotype to the placental pathology in heterozygous Nsdhl deficient female embryos.
a I/LnJ-specific nonsynonymous polymorphism in X-linked Nsdhl, which codes for sterol-4-alpha-carboxylate 3-dehydrogenase in the cholesterol synthesis pathway, causes reduced HDL cholesterol levels in plasma
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
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
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
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
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
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
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
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
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
Investigation of the component reactions of oxidative sterol demethylation. Partial purification of a microsomal sterol 4alpha-carboxylic acid decarboxylase
Identification of a novel polymorphism in X-linked sterol-4-alpha-carboxylate 3-dehydrogenase (Nsdhl) associated with reduced high-density lipoprotein cholesterol levels in I/LnJ mice