PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 18853217-4 2008 CYP51 was cloned from a cDNA library and expressed in both Escherichia coli, where it exhibited high affinity for azole antifungals, and Saccharomyces cerevisiae. Azoles 114-119 sterol 14-demethylase Saccharomyces cerevisiae S288C 0-5 19015352-4 2009 Examination of the ERG11 promoter revealed a conserved azole responsive element that has been shown to be necessary for the transcription factor Upc2p mediated upregulation by azoles in related yeast. Azoles 55-60 sterol 14-demethylase Saccharomyces cerevisiae S288C 19-24 19015352-4 2009 Examination of the ERG11 promoter revealed a conserved azole responsive element that has been shown to be necessary for the transcription factor Upc2p mediated upregulation by azoles in related yeast. Azoles 176-182 sterol 14-demethylase Saccharomyces cerevisiae S288C 19-24 19015352-6 2009 Functional overexpression of ERG11 and ABC1 in Saccharomyces cerevisiae conferred high levels of resistance to azoles and a range of unrelated Abc1p pump substrates, while small molecule inhibitors of Abc1p chemosensitized C. krusei to azole antifungals. Azoles 111-117 sterol 14-demethylase Saccharomyces cerevisiae S288C 29-34 19015352-6 2009 Functional overexpression of ERG11 and ABC1 in Saccharomyces cerevisiae conferred high levels of resistance to azoles and a range of unrelated Abc1p pump substrates, while small molecule inhibitors of Abc1p chemosensitized C. krusei to azole antifungals. Azoles 111-116 sterol 14-demethylase Saccharomyces cerevisiae S288C 29-34 18853217-7 2008 The CYP51 protein exhibited high affinity (k (d) 0.25-0.45 microM) for azole antifungal compounds. Azoles 71-76 sterol 14-demethylase Saccharomyces cerevisiae S288C 4-9 17073780-2 2006 These include the first characterized sterol 14alpha-demethylase P450 (CYP51), a known target for azole and triazole drugs in yeasts and fungi. Azoles 98-103 sterol 14-demethylase Saccharomyces cerevisiae S288C 71-76 18694951-1 2008 Inhibition of sterol-14 alpha-demethylase, a cytochrome P450 (CYP51, Erg11p), is the mode of action of azole antifungal drugs, and with high frequencies of fungal infections new agents are required. Azoles 103-108 sterol 14-demethylase Saccharomyces cerevisiae S288C 62-67 18694951-1 2008 Inhibition of sterol-14 alpha-demethylase, a cytochrome P450 (CYP51, Erg11p), is the mode of action of azole antifungal drugs, and with high frequencies of fungal infections new agents are required. Azoles 103-108 sterol 14-demethylase Saccharomyces cerevisiae S288C 69-75 17073780-6 2006 Atomic structures are available for both Mtb CYP51 and CYP121, revealing modes of azole binding and intriguing mechanistic and structural aspects. Azoles 82-87 sterol 14-demethylase Saccharomyces cerevisiae S288C 45-50 15530358-7 2004 A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics. Azoles 16-21 sterol 14-demethylase Saccharomyces cerevisiae S288C 125-130 16964330-7 2006 The main molecular target of azole antifungals is the cytochrome P-450 protein Erg11p/Cyp51p. Azoles 29-34 sterol 14-demethylase Saccharomyces cerevisiae S288C 79-85 16964330-7 2006 The main molecular target of azole antifungals is the cytochrome P-450 protein Erg11p/Cyp51p. Azoles 29-34 sterol 14-demethylase Saccharomyces cerevisiae S288C 86-92 15530358-7 2004 A mechanism for azole resistance in the yeast pathogen Candida albicans associated with mutations in the ERG11 gene encoding CYP51 is suggested based on CYP51 protein dynamics. Azoles 16-21 sterol 14-demethylase Saccharomyces cerevisiae S288C 153-158 15155210-6 2004 In contrast, MDR1, ERG11, CDR1, and CDR2 were overexpressed in 3, 4, 14, and 35, respectively, of the isolates from patients treated with azoles. Azoles 138-144 sterol 14-demethylase Saccharomyces cerevisiae S288C 19-24 12748589-7 2003 It was reported that ERG11 over-expression had only a modest effect on the development of azole resistance. Azoles 90-95 sterol 14-demethylase Saccharomyces cerevisiae S288C 21-26 12748589-8 2003 However, mutations in the ERG11 gene can cause the resistance, probably by reducing binding of azole to the target enzyme. Azoles 95-100 sterol 14-demethylase Saccharomyces cerevisiae S288C 26-31 12748589-9 2003 We sequenced the ERG11 gene in a high-level azole resistant C. albicans strain, Darlington, and found that two amino acid substitutions, Y132H and I471T, had been encoded in the Darlington ERG11 gene. Azoles 44-49 sterol 14-demethylase Saccharomyces cerevisiae S288C 17-22 12748589-9 2003 We sequenced the ERG11 gene in a high-level azole resistant C. albicans strain, Darlington, and found that two amino acid substitutions, Y132H and I471T, had been encoded in the Darlington ERG11 gene. Azoles 44-49 sterol 14-demethylase Saccharomyces cerevisiae S288C 189-194 12748589-10 2003 To assess the significance of these substitutions, we replaced one of the two copies of ERG11 gene in anazole-susceptible strain of C. albicans with a copy of the Darlington ERG11 and this resulted in a modest increase in azole resistance. Azoles 104-109 sterol 14-demethylase Saccharomyces cerevisiae S288C 88-93 10592714-10 1999 As underlying mechanisms point mutations in the ERG11 gene, encoding for the target enzyme of azoles, as well as energy-dependent efflux mechanisms were identified. Azoles 94-100 sterol 14-demethylase Saccharomyces cerevisiae S288C 48-53 12477804-5 2002 In azole-treated cultures, ERG11 upregulation was preceded by a decrease in ROX1 RNA. Azoles 3-8 sterol 14-demethylase Saccharomyces cerevisiae S288C 27-32 10445042-8 1999 Moreover, the results of molecular electrostatic isopotential (EIP) energy calculations are compatible with the proposed mode of binding between azole antifungal agents and the putative active site of CYP51, although membrane interactions may also have a role in the antifungal activity of azole derivatives. Azoles 145-150 sterol 14-demethylase Saccharomyces cerevisiae S288C 201-206 10445042-8 1999 Moreover, the results of molecular electrostatic isopotential (EIP) energy calculations are compatible with the proposed mode of binding between azole antifungal agents and the putative active site of CYP51, although membrane interactions may also have a role in the antifungal activity of azole derivatives. Azoles 290-295 sterol 14-demethylase Saccharomyces cerevisiae S288C 201-206 12366848-2 2002 Azole activity can be modulated through structural changes in lanosterol demethylase, altered expression of its gene ERG11, alterations in other sterol biosynthesis enzymes or altered expression of multidrug transporters. Azoles 0-5 sterol 14-demethylase Saccharomyces cerevisiae S288C 117-122 11377375-5 2001 In this manuscript, we established through spectral analysis that several azole antifungals bind MT CYP51 with high affinity. Azoles 74-79 sterol 14-demethylase Saccharomyces cerevisiae S288C 100-105 11377375-7 2001 We established a correlation between the affinity of azole compounds to MT CYP51 and their ability to impair the growth of M. bovis and M. smegmatis. Azoles 53-58 sterol 14-demethylase Saccharomyces cerevisiae S288C 75-80 11356139-5 2001 CYP51 has also been discovered in mycobacteria where antifungal azoles have effect and might be of value against tuberculosis. Azoles 64-70 sterol 14-demethylase Saccharomyces cerevisiae S288C 0-5 10445042-0 1999 Molecular modelling of lanosterol 14 alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform: quantitative structure-activity relationships (QSARs) within two related series of antifungal azole derivatives. Azoles 257-262 sterol 14-demethylase Saccharomyces cerevisiae S288C 56-61 10445042-6 1999 Typical azole inhibitors, such as ketoconazole, are able to fit the putative active site of CYP51 by a combination of haem ligation, hydrogen bonding, pi-pi stacking and hydrophobic interactions within the enzyme"s haem environment. Azoles 8-13 sterol 14-demethylase Saccharomyces cerevisiae S288C 92-97 35471041-2 2022 Candida can develop azole drug resistance by overexpression of drug efflux pumps or mutating ERG11, the target of azoles. Azoles 20-25 sterol 14-demethylase Saccharomyces cerevisiae S288C 93-98 35471041-2 2022 Candida can develop azole drug resistance by overexpression of drug efflux pumps or mutating ERG11, the target of azoles. Azoles 114-120 sterol 14-demethylase Saccharomyces cerevisiae S288C 93-98 35471041-9 2022 However, RNA sequencing revealed that C. glabrata Set1 is necessary for azole-induced expression of all 12 genes in the late ergosterol biosynthesis pathway, including ERG11 and ERG3. Azoles 72-77 sterol 14-demethylase Saccharomyces cerevisiae S288C 168-173 35471041-12 2022 Clinical isolates lacking SET1 were also hypersusceptible to azoles which is attributed to reduced ERG11 expression but not defects in drug efflux. Azoles 61-67 sterol 14-demethylase Saccharomyces cerevisiae S288C 99-104 32065093-1 2021 OBJECTIVE(S): Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14alpha-demethylase (CYP51). Azoles 14-19 sterol 14-demethylase Saccharomyces cerevisiae S288C 140-145 35405267-7 2022 Novel azoles in preclinical and clinical stages of development may offer therapeutic advantages due to their greater selectivity of binding to fungal CYP51. Azoles 6-12 sterol 14-demethylase Saccharomyces cerevisiae S288C 150-155 23442154-1 2013 CYP51 encodes the cytochrome P450 sterol 14alpha-demethylase, an enzyme essential for sterol biosynthesis and the target of azole fungicides. Azoles 124-129 sterol 14-demethylase Saccharomyces cerevisiae S288C 0-5 29263059-2 2018 Azole antifungals target the membrane-bound cytochrome P450 monooxygenase lanosterol 14alpha-demethylase (CYP51; Erg11p). Azoles 0-5 sterol 14-demethylase Saccharomyces cerevisiae S288C 106-111 29263059-2 2018 Azole antifungals target the membrane-bound cytochrome P450 monooxygenase lanosterol 14alpha-demethylase (CYP51; Erg11p). Azoles 0-5 sterol 14-demethylase Saccharomyces cerevisiae S288C 113-119 28180188-2 2017 Against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome P450 Cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. Azoles 36-42 sterol 14-demethylase Saccharomyces cerevisiae S288C 97-102 27436465-0 2016 Amino acid substitutions in Erg11p of azole-resistant Candida glabrata: Possible effective substitutions and homology modelling. Azoles 38-43 sterol 14-demethylase Saccharomyces cerevisiae S288C 28-34 26482310-7 2016 Relative increases of azole MICs (from 4- to 32-fold) were observed for fluconazole, voriconazole, and isavuconazole when at least two mutations were present in the same ERG11 allele. Azoles 22-27 sterol 14-demethylase Saccharomyces cerevisiae S288C 170-175 24298976-0 2014 Alterations in the predicted regulatory and coding regions of the sterol 14alpha-demethylase gene (CYP51) confer decreased azole sensitivity in the oilseed rape pathogen Pyrenopeziza brassicae. Azoles 123-128 sterol 14-demethylase Saccharomyces cerevisiae S288C 99-104 24298976-4 2014 By cloning and sequencing the P. brassicae CYP51 (PbCYP51) gene, encoding the azole target sterol 14alpha-demethylase, we identified two non-synonymous mutations encoding substitutions G460S and S508T associated with reduced azole sensitivity. Azoles 78-83 sterol 14-demethylase Saccharomyces cerevisiae S288C 43-48 24298976-4 2014 By cloning and sequencing the P. brassicae CYP51 (PbCYP51) gene, encoding the azole target sterol 14alpha-demethylase, we identified two non-synonymous mutations encoding substitutions G460S and S508T associated with reduced azole sensitivity. Azoles 225-230 sterol 14-demethylase Saccharomyces cerevisiae S288C 43-48 24298976-5 2014 We confirmed the impact of the encoded PbCYP51 changes on azole sensitivity and protein activity by heterologous expression in a Saccharomyces cerevisiae mutant YUG37:erg11 carrying a controllable promoter of native CYP51 expression. Azoles 58-63 sterol 14-demethylase Saccharomyces cerevisiae S288C 41-46 23979758-0 2013 Azole resistance in Cryptococcus gattii from the Pacific Northwest: Investigation of the role of ERG11. Azoles 0-5 sterol 14-demethylase Saccharomyces cerevisiae S288C 97-102 23979758-4 2013 We therefore examined the roles in azole resistance of overexpression of or mutations in the gene (ERG11) encoding the azole target enzyme. Azoles 35-40 sterol 14-demethylase Saccharomyces cerevisiae S288C 99-104 23979758-4 2013 We therefore examined the roles in azole resistance of overexpression of or mutations in the gene (ERG11) encoding the azole target enzyme. Azoles 119-124 sterol 14-demethylase Saccharomyces cerevisiae S288C 99-104 23979758-7 2013 However, the azole MICs for conditional Saccharomyces cerevisiae erg11 mutants expressing the 5 variant ERG11s were within 2-fold of the azole MICs for S. cerevisiae expressing the ERG11 gene from C. gattii R265, non-Pacific Northwest C. gattii strain WM276, or C. neoformans strains H99 or JEC21. Azoles 13-18 sterol 14-demethylase Saccharomyces cerevisiae S288C 65-70 23979758-7 2013 However, the azole MICs for conditional Saccharomyces cerevisiae erg11 mutants expressing the 5 variant ERG11s were within 2-fold of the azole MICs for S. cerevisiae expressing the ERG11 gene from C. gattii R265, non-Pacific Northwest C. gattii strain WM276, or C. neoformans strains H99 or JEC21. Azoles 13-18 sterol 14-demethylase Saccharomyces cerevisiae S288C 104-109 23979758-7 2013 However, the azole MICs for conditional Saccharomyces cerevisiae erg11 mutants expressing the 5 variant ERG11s were within 2-fold of the azole MICs for S. cerevisiae expressing the ERG11 gene from C. gattii R265, non-Pacific Northwest C. gattii strain WM276, or C. neoformans strains H99 or JEC21. Azoles 137-142 sterol 14-demethylase Saccharomyces cerevisiae S288C 65-70 23979758-7 2013 However, the azole MICs for conditional Saccharomyces cerevisiae erg11 mutants expressing the 5 variant ERG11s were within 2-fold of the azole MICs for S. cerevisiae expressing the ERG11 gene from C. gattii R265, non-Pacific Northwest C. gattii strain WM276, or C. neoformans strains H99 or JEC21. Azoles 137-142 sterol 14-demethylase Saccharomyces cerevisiae S288C 104-109 32347094-0 2020 Discovery of Novel Fungal Lanosterol 14alpha-Demethylase (CYP51)/Histone Deacetylase (HDAC) Dual Inhibitors to Treat Azole-resistant Candidiasis. Azoles 117-122 sterol 14-demethylase Saccharomyces cerevisiae S288C 58-63 32347094-4 2020 Herein, the first generation of lanosterol 14alpha-demethylase (CYP51)-histone deacetylase (HDAC) dual inhibitors were designed, which exhibited potent antifungal activity against azole-resistant clinical isolates. Azoles 180-185 sterol 14-demethylase Saccharomyces cerevisiae S288C 64-69 32347094-7 2020 Therefore, CYP51-HDAC dual inhibitors represent a promising strategy to develop novel antifungal agents against azole-resistant candidiasis. Azoles 112-117 sterol 14-demethylase Saccharomyces cerevisiae S288C 11-16 31310805-3 2019 CYP51 reconstitution assays confirmed that AfCYP51A and AfCYP51B as well as three AfCYP51A mutants known to confer azole resistance (G54W, L98H and M220K) were strongly inhibited by both triazoles. Azoles 115-120 sterol 14-demethylase Saccharomyces cerevisiae S288C 0-5 25512882-0 2014 Structural basis for heterogeneous phenotype of ERG11 dependent Azole resistance in C.albicans clinical isolates. Azoles 64-69 sterol 14-demethylase Saccharomyces cerevisiae S288C 48-53 25512882-1 2014 Correlating antifungal Azole drug resistance and mis-sense mutations of ERG11 has been paradoxical in pathogenic yeast Candida albicans. Azoles 23-28 sterol 14-demethylase Saccharomyces cerevisiae S288C 72-77 25512882-4 2014 To analyze role of mis-sense mutations on Azole resistance energetically optimized, structurally validated homology model of wild C.albicans ERG11 using eukaryotic template was generated. Azoles 42-47 sterol 14-demethylase Saccharomyces cerevisiae S288C 141-146 23480635-0 2013 Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans. Azoles 32-37 sterol 14-demethylase Saccharomyces cerevisiae S288C 0-5 23480635-2 2013 One mechanism of azole resistance involves point mutations in the ERG11 gene, which encodes the target enzyme (cytochrome P450 lanosterol 14alpha-demethylase). Azoles 17-22 sterol 14-demethylase Saccharomyces cerevisiae S288C 66-71 23480635-5 2013 We further verified the contribution of the amino acid substitutions to azole resistance using site-directed mutagenesis of the ERG11 gene to recreate these mutations for heterologous expression in Saccharomyces cerevisiae. Azoles 72-77 sterol 14-demethylase Saccharomyces cerevisiae S288C 128-133 23221625-10 2013 In contrast, the azole-resistant isolates overexpressed ERG11 and showed increased ergosterol content. Azoles 17-22 sterol 14-demethylase Saccharomyces cerevisiae S288C 56-61 23221625-11 2013 Moreover, the isolates resistant to three azole antifungals expressed higher levels of ERG11 mRNA than those resistant to only fluconazole or itraconazole. Azoles 42-47 sterol 14-demethylase Saccharomyces cerevisiae S288C 87-92 23221625-12 2013 Two ERG11 mutations, Y132F and S154F, were found in azole-resistant isolates and could be shown to mediate azole resistance by expression in S. cerevisiae. Azoles 52-57 sterol 14-demethylase Saccharomyces cerevisiae S288C 4-9 23221625-12 2013 Two ERG11 mutations, Y132F and S154F, were found in azole-resistant isolates and could be shown to mediate azole resistance by expression in S. cerevisiae. Azoles 107-112 sterol 14-demethylase Saccharomyces cerevisiae S288C 4-9 23221625-13 2013 CONCLUSIONS: The up-regulation and mutations of ERG11 mediate azole resistance of C. tropicalis. Azoles 62-67 sterol 14-demethylase Saccharomyces cerevisiae S288C 48-53 21478305-0 2011 Impact of recently emerged sterol 14{alpha}-demethylase (CYP51) variants of Mycosphaerella graminicola on azole fungicide sensitivity. Azoles 106-111 sterol 14-demethylase Saccharomyces cerevisiae S288C 57-62 22615293-5 2012 Haploinsufficiency profiling of these compounds in S. cerevisiae suggests that they target Erg11p, a cytochrome P450 family member, which is the target of azoles. Azoles 155-161 sterol 14-demethylase Saccharomyces cerevisiae S288C 91-97 22615293-8 2012 We modeled the Erg11p protein based on the human CYP51 crystal structure, and in silico docking of these compounds suggests that they interact with the heme center in a manner similar to that of azoles. Azoles 195-201 sterol 14-demethylase Saccharomyces cerevisiae S288C 15-21 22615293-9 2012 Consistent with these docking observations, Candida strains carrying azole-resistant alleles of ERG11 are also resistant to the compounds in this study. Azoles 69-74 sterol 14-demethylase Saccharomyces cerevisiae S288C 96-101 22615293-10 2012 Thus, we have identified non-azole Erg11p inhibitors, using a systematic approach for ligand and target characterization. Azoles 29-34 sterol 14-demethylase Saccharomyces cerevisiae S288C 35-41 21478305-1 2011 The progressive decline in the effectiveness of some azole fungicides in controlling Mycosphaerella graminicola, causal agent of the damaging Septoria leaf blotch disease of wheat, has been correlated with the selection and spread in the pathogen population of specific mutations in the M. graminicola CYP51 (MgCYP51) gene encoding the azole target sterol 14alpha-demethylase. Azoles 53-58 sterol 14-demethylase Saccharomyces cerevisiae S288C 302-307 21478305-4 2011 We introduced individual and combinations of identified alterations by site-directed mutagenesis and functionally determined their impact on azole sensitivity by expression in a Saccharomyces cerevisiae mutant YUG37::erg11 carrying a regulatable promoter controlling native CYP51 expression. Azoles 141-146 sterol 14-demethylase Saccharomyces cerevisiae S288C 274-279 20305029-1 2010 The recent decrease in the sensitivity of the Western European population of the wheat pathogen Mycosphaerella graminicola to azole fungicides has been associated with the emergence and subsequent spread of mutations in the CYP51 gene, encoding the azole target sterol 14alpha-demethylase. Azoles 126-131 sterol 14-demethylase Saccharomyces cerevisiae S288C 224-229 20305029-1 2010 The recent decrease in the sensitivity of the Western European population of the wheat pathogen Mycosphaerella graminicola to azole fungicides has been associated with the emergence and subsequent spread of mutations in the CYP51 gene, encoding the azole target sterol 14alpha-demethylase. Azoles 249-254 sterol 14-demethylase Saccharomyces cerevisiae S288C 224-229 20305029-8 2010 These findings demonstrate, for the first time for a plant pathogenic fungus, the impacts that naturally occurring CYP51 alterations have on both azole sensitivity and intrinsic protein function. Azoles 146-151 sterol 14-demethylase Saccharomyces cerevisiae S288C 115-120