AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation Science
SterolsSterol 14-DemethylaseHistone DemethylasesJumonji Domain-Containing Histone DemethylasesOxidoreductases, N-DemethylatingCytochrome P-450 CYP3ALanosterolRetinoblastoma-Binding Protein 2Cytochrome P-450 Enzyme SystemMethylationHistonesCytochrome P-450 CYP2D6Cytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2ErgosterolPhytosterolsOxidoreductases, O-DemethylatingCholestadienolsOxidoreductasesMolecular Sequence DataSterol Regulatory Element Binding Protein 1CholesterolAminopyrine N-DemethylaseLysineMicrosomes, LiverAryl Hydrocarbon HydroxylasesSterol Regulatory Element Binding Protein 2Histone-Lysine N-MethyltransferaseAzolesStigmasterolMixed Function OxygenasesAmino Acid SequenceMutationBiosynthetic PathwaysEpigenesis, GeneticAniline HydroxylaseKetoconazoleDesmosterolVanillic AcidLiverF-Box ProteinsSqualeneSubstrate SpecificityBase SequenceCytochrome P-450 CYP2B1CholestenesSulfonium CompoundsTranylcypromineKineticsDehydrocholesterolsTranscription, GeneticSteroid HydroxylasesPromoter Regions, GeneticGene Expression Regulation, EnzymologicCholestanetriol 26-MonooxygenaseRNA, Messenger14-alpha Demethylase InhibitorsMicrosomesMevalonic AcidMolecular StructureCloning, MolecularSterol Regulatory Element Binding ProteinsStreptomycesRepressor ProteinsCholestanesSequence Homology, Amino AcidTranscription FactorsNitroanisole O-DemethylaseHydroxymethylglutaryl CoA ReductasesMiconazoleDealkylationChromatin ImmunoprecipitationGene Expression Regulation, PlantPargylineHydroxylationGas Chromatography-Mass SpectrometryAntifungal AgentsProtein BindingEnzyme InhibitorsEnzyme InductionArabidopsisCell LineCells, CulturedChromatinRecombinant ProteinsGene Expression RegulationMultigene FamilyBiocatalysisCytochrome P-450 CYP2E1Chromatography, Thin LayerDNA-Binding ProteinsEconazoleHydroxycholesterolsProtein Structure, TertiaryBacterial ProteinsSequence AlignmentDNA MethylationSaccharomyces cerevisiaeChromatography, High Pressure LiquidEscherichia coli
LanosterolEukaryotic membranesOxidoreductaseCytochrome P450Squalene synthaseEnzymeOverexpressionInhibitFungalCompoundsCompoundAzolesEnzymesCatalyzesSteroidsHemeErgosterolSpeciesReactionFamilyInhibitionLanosterol 14-demethylaseAzoleERG11DemethylationEnzymesSynthesisFungiMembrane permeabilityNADPHIntermediatesAntifungalInteractionsResults
Lanosterol4
  • Although the lanosterol 14α-demethylase is present in a wide variety of organisms, the enzyme is studied primarily in the context of fungi, where it plays an essential role in mediating membrane permeability. (wikipedia.org)
  • In fungi, CYP51 catalyzes the demethylation of lanosterol to create an important precursor that is eventually converted into ergosterol. (wikipedia.org)
  • Other names in common use include obtusufoliol 14-demethylase, lanosterol 14-demethylase, lanosterol 14alpha-demethylase, and sterol 14alpha-demethylase. (wikipedia.org)
  • Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive protein (CRP), lanosterol 14 α -demethylase (LDM), squalene synthase (SqS) and farnesiod X-receptor (FXR) known to be implicated in the physiology of hyperlipidemia. (springeropen.com)
Eukaryotic membranes1
  • Sterols represent the signature of eukaryotic membranes as well as serve as regulatory molecules that control growth and development processes. (vanderbilt.edu)
Oxidoreductase1
  • The systematic name of this enzyme class is sterol,NADPH:oxygen oxidoreductase (14-methyl cleaving). (wikipedia.org)
Cytochrome P4503
  • In enzymology, a sterol 14-demethylase (EC 1.14.13.70) is an enzyme of the Cytochrome P450 (CYP) superfamily. (wikipedia.org)
  • The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. (biomedcentral.com)
  • The most commonly used groups of antifungal agents are the polyenes (e.g., amphotericin B), which disrupt membrane function by direct association with fungal sterols, and the azoles (fluconazole, itraconazole, voriconazole and posaconazole), which inhibit sterol biosynthesis in a step catalysed by the cytochrome P450-dependent C14α-demethylase [ 3 ]. (biomedcentral.com)
Squalene synthase1
  • Squalene synthase (SQS) is a key enzyme in sterol biosynthesis that catalyses an unusual head-to-head condensation of two molecules of farnesyl pyrophosphate in a two-step reaction to produce squalene, which is the first committed step in sterol biosynthesis. (biomedcentral.com)
Enzyme3
  • This enzyme, orthologs of which are found in all biological kingdoms, is regarded as a possible ancestor to all P450 superfamily and is absolutely required for sterol biosynthesis. (vanderbilt.edu)
  • This enzyme participates in biosynthesis of steroids. (wikipedia.org)
  • Aromatase , also called estrogen synthetase or estrogen synthase , is an enzyme responsible for a key step in the biosynthesis of estrogens . (wikidoc.org)
Overexpression2
  • Mutations in the coding region of CYP51 genes, overexpression of CYP51, and overexpression of membrane efflux transporters can all lead to resistance to these antifungals. (wikipedia.org)
  • Lack of an Intron in Cytochrome b and Overexpression of Sterol 14 alpha-Demethylase Indicate a Potential Risk for QoI and DMI Resistance Development in Neophysopella spp. (rothamsted.ac.uk)
Inhibit1
  • Because ergosterol constitutes a fundamental component of fungal membranes, many antifungal medications have been developed to inhibit 14α-demethylase activity and prevent the production of this key compound. (wikipedia.org)
Fungal2
  • Determination of fungal CYP51 structures will broaden the options for CYP51-targeted antifungals, which is highly desirable due to ever increasing fungal drug resistance, especially in immunosuppressed, e.g. post-cancer patients. (vanderbilt.edu)
  • Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. (biomedcentral.com)
Compounds3
  • At the amino acid sequence identity across the kingdoms as low as 22-27%, all CYP51 family members catalyze one essentially the same three-step reaction of the oxidative removal of the 14α-methyl group from sterol precursors, enabling the formation of cholesterol in humans vs. ergosterol/egrosterol-like compounds in human pathogens. (vanderbilt.edu)
  • These compounds bind as the sixth ligand to the heme group in CYP51, thereby altering the structure of the active site and acting as noncompetitive inhibitors. (wikipedia.org)
  • A new fructofuranoside glycerol, dryoptkirbioside (1), along with thirteen known compounds (2-14), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. (bvsalud.org)
Compound1
  • Our preliminary data suggest that the derivative of this compound, designed to fill the deepest portion of the CYP51 substrate binding cavity, has even higher antiparasitic potency, especially in the drug-resistant strains of T. cruzi and in Leishmania . (vanderbilt.edu)
Azoles1
  • Coordination of azoles to the prosthetic heme group in the enzyme's active site causes a characteristic shift in CYP51 absorbance, creating what is commonly referred to as a type II difference spectrum. (wikipedia.org)
Enzymes1
  • These sterols localize to the plasma membrane of cells, where they play an important structural role in the regulation of membrane fluidity and permeability and also influence the activity of enzymes, ion channels, and other cell components that are embedded within. (wikipedia.org)
Catalyzes1
  • It catalyzes the last steps of estrogen biosynthesis from androgens (specifically, it transforms androstenedione to estrone and testosterone to estradiol ). (wikidoc.org)
Steroids1
Heme1
  • The free-living nematode Caenorhabditis eleganslacks the capacity to synthesize heme but is able to take it from the cytochromes respiration sterols protist bacteria it feeds on (15). (medicinelakex1.com)
Ergosterol1
Species1
  • Those groups with only one CYP51 per species are all called by one name: CYP51A1 is for all animal CYP51s since they are orthologous. (wikipedia.org)
Reaction2
  • As a result, the CYP51 reaction is the major target for clinical and agricultural antifungals and is very likely to become a successful target for treatment of human infections with protozoan pathogens. (vanderbilt.edu)
  • The structures provide insights into the molecular basis of the CYP51 reaction mechanism and strict functional conservation and will serve as the templates for rational design of more efficient pathogen-specific drugs. (vanderbilt.edu)
Family2
  • The CYP51 family (sterol 14α-demethylase) certainly belongs to the second group. (vanderbilt.edu)
  • It is any member of the CYP51 family. (wikipedia.org)
Inhibition5
  • The mechanism is unknown but inhibition of mammalian CYP51 as well as other CYPs, e.g. (ncats.io)
  • The inhibition of CYP51 would cause a reduction of the endogenous concentrations of ergosterol and an accumulation of lanosterol and other 14-methyl sterols, thus inhibiting the growth of fungal cells. (abt737.com)
  • At fungi static levels the main effect is inhibition of ergosterol synthesis but at higher concentrations there is an additional mechanism of membrane damage unrelated to sterol synthesis. (com.bd)
  • Clotrimazole causes inhibition of ergosterol biosynthesis, an essential constituent of fungal cell membranes. (com.bd)
  • Though decreased ergosterol, due to the inhibition of lanosterol 14-demethylase (also known as CYP51) is accepted to be primarily responsible for the antimycotic properties of clotrimazole, this drug also shows other pharmacological effects. (com.bd)
Lanosterol 14-demethylase1
  • Other names in common use include obtusufoliol 14-demethylase, lanosterol 14-demethylase, lanosterol 14alpha-demethylase, and sterol 14alpha-demethylase. (wikipedia.org)
Azole3
  • The effectiveness of imidazoles and triazoles (common azole subclasses) as inhibitors of 14α-demethylase have been confirmed through several experiments. (wikipedia.org)
  • Other studies employ spectrophotometry to quantify azole-CYP51 interactions. (wikipedia.org)
  • Azole antifungal agents inhibit fungal lanosterol 14α-demethylase (CYP51), which is involved in the biosynthesis of ergosterol, a significant cellular membrane component. (abt737.com)
ERG114
  • It has been proved that the C-14 demethylation of lanosterol is essential due to the fact either disruption of erg11 in S. cerevisiae or deletion of A. fumigatus erg11A and erg11B (the homologous genes of S. cerevisiae erg11) results in lethal cells (246). (idhinhibitor.com)
  • Cytochrome P450 enzymes (P450s), like 14-a-sterol demethylase (Erg11) on the ergosterol biosynthetic pathway, belong for the classical mono-oxygenases that happen to be present in all kingdoms of life (30, 31). (idhinhibitor.com)
  • ERG11 catalyses two successive hydroxylations of the 14alpha-methyl group, followed by its elimination as a Formate moiety, leaving a 14(15) double bond (KEGG ) - a key step in biosynthesis of Ergosterol (Klein et al. (springeropen.com)
  • Though similar to cholesterol synthesis in mammals the pathway for Ergosterol biosynthesis differs in some obvious ways (Hitchcock, 1993 ) and so ERG11 was targeted for management of this eukaryotic pathogen in its eukaryotic human host. (springeropen.com)
Demethylation1
Enzymes2
  • These sterols localize to the plasma membrane of cells, where they play an important structural role in the regulation of membrane fluidity and permeability and also influence the activity of enzymes, ion channels, and other cell components that are embedded within. (wikipedia.org)
  • Sterol 14α-demethylase (CYP51) is one of the key enzymes of sterol biosynthesis in the biological kingdom and a prime target of antifungal drugs. (nih.gov)
Synthesis1
  • Based on GO and KEGG annotations, we identified transcripts related to sulfur metabolism, sterol biosynthesis, trehalose synthesis, and hydrolysis. (biomedcentral.com)
Fungi2
  • The demethylated products of the CYP51 reaction are vital intermediates in pathways leading to the formation of cholesterol in humans, ergosterol in fungi, and other types of sterols in plants. (wikipedia.org)
  • The sterol accumulation areas are called sterol-rich plasma membrane domains (SRDs) and happen to be reported to take part in polarized development in fungi. (idhinhibitor.com)
Membrane permeability1
  • The membrane damaging effects of PB were attributed to binding with ergosterol to increase membrane permeability and interfering ergosterol biosynthesis involved with the reduction of SE and CYP51 activities. (hindawi.com)
NADPH1
  • Enzima P450 dependiente de NADPH que desempeña un papel esencial en la vía biosintética de los esteroles al catalizar la desmetilación de los 14-metil esteroles tales como el lanosterol. (bvsalud.org)
Intermediates1
  • MAS are intermediates in the biosynthesis of cholesterol and may have a signaling role in initiating meiosis and oocyte maturation. (ncats.io)
Antifungal1
  • Further mechanistic investigations showed that the potent antifungal activity of novel compound 13s might act by inhibiting the CYP51 of Candida albicans. (abt737.com)
Interactions1
  • Based on the interactions between compound 1 and A. fumigatus CYP51, the benzothiazole ring was replaced by benzoheterocycles to facilitate the formation of hydrogen bond interactions with Tyr122 of CYP51. (abt737.com)
Results1
  • Results: ten RCTs involving 1,052 patients were included in the meta-analysis, including 573 patients in the EIN group and 479 patients in the enteral nutrition (EN) group. (bvsalud.org)