Any feedback?
Information on EC 1.14.14.154 - sterol 14alpha-demethylase and Organism(s) Candida albicans and UniProt Accession P10613
for references in articles please use BRENDA:EC1.14.14.154Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.14.14.154 sterol 14alpha-demethylaseIUBMB Comments
This cytochrome P-450 (heme-thiolate) enzyme acts on a range of steroids with a 14alpha-methyl group, such as obtusifoliol and lanosterol. The enzyme catalyses a hydroxylation and a reduction of the 14alpha-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.
Specify your search results
Word Map
- 1.14.14.154
- azole
- candida
- fluconazole
- aspergillus
- fumigatus
- albicans
- ergosterol
- voriconazole
- itraconazole
-
azole-resistant
-
fungicide
- triazole
- posaconazole
- cholesterol
- aspergillosis
- ketoconazole
-
microdilution
- candidiasis
-
fluconazole-resistant
- amphotericin
- glabrata
-
cross-resistance
- tebuconazole
-
echinocandins
-
eucast
- parapsilosis
- tropicalis
-
isavuconazole
- agriculture
-
araf
-
vulvovaginal
- clotrimazole
- drug development
-
stricto
-
mycology
- digitatum
-
etest
- propiconazole
- prochloraz
- graminicola
- micafungin
-
non-albicans
- krusei
-
cholesterogenic
- caspofungin
- benznidazole
- pharmacology
- anidulafungin
-
mycosphaerella
- terbinafine
- auris
- candidemia
- tubingensis
- medicine
The taxonomic range for the selected organisms is: Candida albicans
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
cyp51, erg11, cyp51a, cyp51a1, erg11p, cyp51b, lanosterol 14alpha-demethylase, lanosterol 14 alpha-demethylase, lanosterol demethylase, sterol 14alpha-demethylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
14-demethylase
-
-
-
-
14alpha-demethylase
14alpha-methylsterol 14alpha-demethylase
-
-
-
-
14alpha-sterol demethylase
-
-
-
-
14DM
-
-
-
-
CYP51
CYPL1
-
-
-
-
cytochrome CYP51
-
-
-
-
cytochrome P 450 CYP51
-
-
-
-
cytochrome P-450 lanosterol 14alpha-demethylase
-
-
-
-
cytochrome P-450-dependent 14alpha-sterol demethylase
-
-
-
-
cytochrome P-450-dependent obtusifoliol 14alpha-demethylase
-
-
-
-
cytochrome P-450/14DM
-
-
-
-
cytochrome P-45014DM
-
-
-
-
cytochrome P450 14DM
-
-
-
-
cytochrome P450 51
-
-
-
-
cytochrome P450 CYP51
-
-
-
-
cytochrome-P450 14alpha-demethylase
-
-
-
-
demethylase, methylsterol 14alpha-
-
-
-
-
eburicol 14 alpha-demethylase
-
-
-
-
eburicol 14alpha-demethylase
-
-
-
-
lanosterol 14 alpha-demethylase
-
-
-
-
lanosterol 14-demethylase
-
-
-
-
lanosterol 14alpha-demethylase
lanosterol 14alpha-methyldemethylase
-
-
-
-
lanosterol C-14 demethylase
-
-
-
-
lanosterol demethylase
-
-
-
-
LDM
-
-
-
-
methylsterol 14alpha-demethylase (P 450 CYP51)
-
-
-
-
Obtusifoliol 14-alpha demethylase
-
-
-
-
obtusifoliol 14-demethylase
-
-
-
-
obtusifoliol 14alpha-demethylase
-
-
-
-
obtusifoliol-metabolizing 14alpha-demethylase
-
-
-
-
obtusufoliol 14-demethylase
-
-
-
-
P 450 lanosterol C-14 demethylase
-
-
-
-
P-450 lanosterol demethylase
-
-
-
-
P-45014DM
-
-
-
-
P-45014DM-containing monooxygenase system
-
-
-
-
P-450OBT 14DM
-
-
-
-
P450(14DM)
-
-
-
-
P450-14DM
-
-
-
-
P450-L1A1
-
-
-
-
P45014DM
-
-
-
-
sterol 14-demethylase
-
-
-
-
sterol 14-demethylase P450
-
-
-
-
sterol 14alpha-demethylase
sterol 14alpha-demethylase (CYP51)
-
-
-
-
sterol C14 demethylase
-
-
-
-
additional information
14alpha-demethylase
-
-
-
-
CYP51
-
-
-
-
lanosterol 14alpha-demethylase
-
-
-
-
sterol 14alpha-demethylase
-
-
-
-
additional information
-
CYP51 is a member of the cytochrome P450 superfamily
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 14alpha-methylsteroid + 3 [reduced NADPH-hemoprotein reductase] + 3 O2 = a DELTA14-steroid + formate + 3 [oxidized NADPH-hemoprotein reductase] + 4 H2O
active site structure, structure-function relationship
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxygenation
-
-
-
-
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
hydroxylation
-
-
-
-
monooxygenation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
sterol,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (14-methyl cleaving)
This cytochrome P-450 (heme-thiolate) enzyme acts on a range of steroids with a 14alpha-methyl group, such as obtusifoliol and lanosterol. The enzyme catalyses a hydroxylation and a reduction of the 14alpha-methyl group, followed by a second hydroxylation, resulting in the elimination of formate and formation of a 14(15) double bond.
CAS REGISTRY NUMBER
COMMENTARY
138674-19-8
deleted registry number
341989-59-1
deleted registry number
60063-87-8
-
90463-45-9
deleted registry number
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethylcholesta-8,14,24-trien-3-ol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
?
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
24-methylenedihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
-
-
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethylcholesta-8,14,24-trien-3-ol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
8-lanosta-3beta-ol
-
-
?
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
DHL
-
-
?
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
8-lanosten-3beta-ol
-
-
?
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14-dien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
4,4,14alpha-trimethyl-5alpha-cholesta-8-en-3beta-ol
-
-
?
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
-
-
-
?
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
the enzyme is involved in ergosterol and cholesterol biosynthesis
-
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
lanosta-8,24-dien-3beta-ol
-
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
4,4,14alpha-trimethyl-5alpha-cholesta-8,24-dien-3beta-ol
-
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
-
production of follicular fluid-meiosis activating steroid by lanosterol demethylation
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
the enzyme is involved in ergosterol and cholesterol biosynthesis
-
-
?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
low activity
-
-
?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
preferred substrate
-
-
?
additional information
?
-
-
enzyme of sterol biosynthesis, sterol 14-demethylation occurs in all organism exhibiting de novo sterol biosynthesis
-
-
?
additional information
?
-
-
the regio- and stereospecific 14alpha-demethylation CYP51 reaction proceeds in three steps, each requiring one molecule of oxygen and two NADPH-derived reducing equivalents, via 14alpha-carboxyalcohol and 14alpha-carboxyaldehyde intermediates, cleavage of the the C-C bond by radical or Bayer-Villiger mechanism, DELTA14,15 double bond introduction into the sterol core
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
24,25-dihydrolanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
the enzyme is involved in ergosterol and cholesterol biosynthesis
-
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
4,4-dimethylcholesta-8,14,24-trien-3-ol + [oxidized NADPH-hemoprotein reductase] + H2O
-
-
-
-
?
obtusifoliol + [reduced NADPH-hemoprotein reductase] + O2
4alpha-methyl-5alpha-ergost-8,14,24(28)-trien-3beta-ol + formate + [oxidized NADPH-hemoprotein reductase] + H2O
-
low activity
-
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
-
production of follicular fluid-meiosis activating steroid by lanosterol demethylation
-
?
lanosterol + [reduced NADPH-hemoprotein reductase] + O2
?
-
the enzyme is involved in ergosterol and cholesterol biosynthesis
-
-
?
additional information
?
-
-
enzyme of sterol biosynthesis, sterol 14-demethylation occurs in all organism exhibiting de novo sterol biosynthesis
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH-hemoprotein reductase
A flavoprotein containing both FMN and FAD. This enzyme catalyses the transfer of electrons from NADPH, an obligatory two-electron donor, to microsomal P-450 monooxygenases, EC 1.14.14._
-
NADPH-hemoprotein reductase
A flavoprotein containing both FMN and FAD. This enzyme catalyses the transfer of electrons from NADPH, an obligatory two-electron donor, to microsomal P-450 monooxygenases, EC 1.14.14._
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-[5-(2,4-difluoro-phenyl)-5-imidazol-1-ylmethyl-tetrahydro-furan-3-yl]-1-isopropyl-butylamine
0.0001 mM, wild-type, 10% residual activity, mutant F145L, 35% residual activity, mutant Y132H, 60% residual activity
4-[5-(2,4-difluoro-phenyl)-5-[1,2,4]triazol-1-ylmethyl-tetrahydro-furan-3-yl]-1-isopropyl-butylamine
0.0001 mM, wild-type, 25% residual activity, mutant F145L, 75% residual activity, mutant Y132H, 75% residual activity
6-[5-(2,4-difluoro-phenyl)-5-imidazol-1-ylmethyl-tetrahydro-furan-3-yl]-2-methyl-hexan-3-one
0.0001 mM, wild-type, no residual activity, mutant F145L, 5% residual activity, mutant Y132H, 25% residual activity
6-[5-(2,4-difluoro-phenyl)-5-[1,2,4]triazol-1-ylmethyl-tetrahydro-furan-3-yl]-2-methyl-hexan-3-one
0.0001 mM, wild-type, no residual activity, mutant F145L, 15% residual activity, mutant Y132H, 55% residual activity
(R)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol
i.e. oteseconazole, i.e. VT-1161. 98% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[4-(2-fluoro-4-amino-phenyl)-piperazin-1-yl]-propan-2-ol
-
-
1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[4-(2-fluoro-4-nitrophenyl)-piperazin-1-yl]-propan-2-ol
-
-
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(2-bromobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(2-chlorobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(2-fluorobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(2-methylbenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(3-chlorobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(3-fluorobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(4-bromobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(4-chlorobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(4-ethylbenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(4-fluorobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(4-methylbenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-(4-nitrobenzyl)-amino]-2-propanol
-
exhibits higher activity than fluconazole
1-(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-[N-allyl-N-benzyl-amino]-2-propanol
-
exhibits higher activity than fluconazole
2,4-dichloro-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
2-bromo-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
2-chloro-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
3-bromo-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
3-chloro-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
3-nitrophenyl-4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)-propyl]-amino)-methyl)-benzoate
-
exhibits higher activity than fluconazole
4-butyl-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
4-chloro-N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
4-nitrophenyl-4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)-propyl]-amino)-methyl)-benzoate
-
exhibits higher activity than fluconazole
4-tert-butyl-N-(4-[4-[2-(2,4-difluorophenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-benzamide
-
-
butyl-4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazole-1-yl)-propyl]-amino)-methyl)-benzoate
-
exhibits higher activity than fluconazole
ethyl-4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazole-1-yl)-propyl]-amino)-methyl)-benzoate
-
exhibits higher activity than fluconazole
isopropyl-4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazole-1-yl)-propyl]-amino)-methyl)-benzoate
-
exhibits higher activity than fluconazole
methyl-2-[4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)-propyl]-amino)-methyl)-benzoyloxy]-benzoate
-
exhibits higher activity than fluconazole
methyl-4-((allyl[2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazole-1-yl)-propyl]-amino)-methyl)-benzoate
-
exhibits higher activity than fluconazole
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-2,4-dimethyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-2-methoxy-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-2-nitro-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-3,4,5-trimethoxy-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-3,4-dimethoxy-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-3,4-dimethyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-3-methoxy-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-3-methyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-3-trifluoromethyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-ethyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-isopropyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-methoxy-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-methyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-nitro-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-pentyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-propyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluoro-phenyl)-4-trifluoromethoxy-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluorophenyl)-2-fluoro-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluorophenyl)-2-methyl-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluorophenyl)-4-fluoro-benzamide
-
-
N-(4-[4-[2-(2,4-difluoro-phenyl)-2-hydroxy-3-[1H-1,2,4]triazol-1-yl-propyl]-piperazin-1-yl]-3-fluorophenyl)-benzamide
-
-
posaconazole
98% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
triazole
-
sensitive and resistant variants of CYP51A1, mutations lead to alterations in the enzyme as drug target, primary determinants of triazole resistance, overview
clotrimazole
78% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
fluconazole
-
binds to the active site of CYP51 via coordination of the N atom of the triazole nucleus with iron of the heme group
fluconazole
54% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
fluconazole
N136Y transformants show a reduced in vitro susceptibility to fluconazole compared to wild-type controls. The amino acid substitution N136Y in Candida albicans sterol 14alpha-demethylase is involved in fluconazole resistance
itraconazole
91% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
ketoconazole
85% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
miconazole
79% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
voriconazole
84% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
additional information
-
design of non-azole antifungal lead compounds based on the constructed three-dimensional model of CYP51by coupling structure-based de novo design, overview
-
additional information
-
inhibitory potency of fungicides, antifungal drugs, and cytostatic drugs, overview
-
additional information
-
inhibitory potency, antifungal activity in vivo, and structure-function analysis of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted phenyl)-piperazin-1-yl]-propan-2-ol derivatives, overview
-
additional information
-
inhibition of CYP51 involves a coordination bond with iron of the heme group, the hydrophilic H-bonding region, the hydrophobic region, and the narrow hydrophobic cleft
-
additional information
-
yeast cells are more sensitive to azole drugs than mammalian cells, yeast cells have lower P450 enzyme content and a higher IC50 value
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0063
lanosterol
pH and temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
comparison of CYP51 family enzyme structures, overview
additional information
-
three-dimensional structure analysis: the S1 subsite is the hydrophilic hydrogen-bonding region, the S2 subsite is the hydrophobic region, the S3 subsite is the narrow hydrophobic cleft formed by the residues in the helix B'-meander1 loop and the N-terminus of helix I, the S4 subsite adjacent to the beta6-1/beta1-4 sheet is another important hydrogen-bonding region in the active site, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
building up of homology models based on crystal coordinates of enzyme in complex with inhibitors 4-phenylimidazole or fluconazole, modeling of substrate 24-methylene-24,25-dihydrolanosterol into active site
-
crystals are grown using a hanging drop vapor diffusion technique. Enzyme complexes with posaconazole and VT-1161 are crystallized in the monoclinic C121 space group, and the structures are refined to 2.86 and 2.0 A. X-ray structures of Candida albicans CYP51 complexes with posaconazole and VT-1161, providing a molecular mechanism for the potencies of these drugs
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D116E
the azole Kd value of the mutant enzyme is little altered compared to the wild type enzyme
F105L
the azole Kd value of the mutant enzyme is little altered compared to the wild type enzyme
F145L
significant modification of heme environment as judged from spectral properties, about 45% of wild-type activity, resistant to azoles
R467K
the azole Kd value of the mutant enzyme is little altered compared to the wild type enzyme
Y132H
K143R
-
the mutant shows a sustained capacity for producing ergosterol, even in the presence of fluconazole
N136Y
N136Y transformants show a reduced in vitro susceptibility to fluconazole compared to wild-type controls. The amino acid substitution N136Y in Candida albicans sterol 14alpha-demethylase is involved in fluconazole resistance
V456I
-
the mutation leads to an 8fold increase in fluconazole minimal inhibitory concentrations of Pichia pastoris mutants compared to the wild type controls. The mutant shows a sustained capacity for producing ergosterol, even in the presence of fluconazole
Y118A
-
site-directed mutagenesis, the mutant shows reduced actalytic activity an reduced azole susceptibility compared to the wild-type enzyme
Y118F
-
site-directed mutagenesis, the mutant shows reduced actalytic activity an reduced azole susceptibility compared to the wild-type enzyme
Y118T
-
site-directed mutagenesis, the mutant shows reduced actalytic activity an reduced azole susceptibility compared to the wild-type enzyme
Y447H
-
the mutation leads to an 8fold increase in fluconazole minimal inhibitory concentrations of Pichia pastoris mutants compared to the wild type controls. The mutant shows a sustained capacity for producing ergosterol, even in the presence of fluconazole
Y132H
significant modification of heme environment as judged from spectral properties, about 50% of wild-type activity, resistant to azoles
Y132H
the azole Kd value of the mutant enzyme is clearly altered compared to the wild type enzyme
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Spodoptera frugiperda Sf9 cell membranes under control of the p10 promoter using the baculovirus transfection system
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
fluconazole-resistant strain isolated from patients receiving long-term azole treatment shows Y132H and F145L substitutions
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bak, S.; Kahn, R.A.; Olsen, C.E.; Halkier, B.A.
Cloning and expression in Escherichia coli of the obtusifoliol 14alpha-demethylase of Sorghum bicolor (L.) Moench, a cytochrome P450 orthologous to the sterol 14alpha-demethylases (CYP51) from fungi and mammals
Plant J.
11
191-201
1997
Arabidopsis thaliana, Saccharomyces cerevisiae, Candida albicans, [Candida] glabrata, Candida tropicalis, Homo sapiens, Manihot esculenta, no activity in Escherichia coli, Penicillium italicum, Rattus norvegicus, Schizosaccharomyces pombe, Sinapis alba, Sorghum bicolor, Ustilago maydis, Zea mays, Sinapis alba L.
Aoyama, Y.; Funae, Y.; Noshiro, M.; Horiuchi, T.; Yoshida, Y.
Occurrence of a P450 showing high homology to yeast lanosterol 14-demethylase (P45014DM) in the rat liver
Biochem. Biophys. Res. Commun.
201
1320-1326
1994
Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, Embryophyta, Rattus norvegicus
Van Nistelrooy, J.G.M.; Van den Brink, J.M.; Van Kan, J.A.L.; Van Gorcom, R.F.M.; de Waard, M.A.
Isolation and molecular characterisation of the gene encoding eburicol 14alpha-demethylase (CYP51) from Penicillium italicum
Mol. Gen. Genet.
250
725-733
1996
Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, Penicillium italicum
Aoyama, Y.; Noshiro, M.; Gotoh, O.; Imaoka, S.; Funae, Y.; Kurosawa, N.; Horiuchi, T.; Yoshida, Y.
Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species
J. Biochem.
119
926-933
1996
Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, Embryophyta, Homo sapiens, Penicillium italicum, Rattus norvegicus, Schizosaccharomyces pombe, Ustilago maydis
Kudo, M.; Ohi, M.; Aoyama, Y.; Nitahara, Y.; Chung, S.K.; Yoshida, Y.
Effects of Y132H and F145L substitutions on the activity, azole resistance and spectral properties of Candida albicans sterol 14-demethylase P450 (CYP51): a live example showing the selection of altered P450 through interaction with environmental compounds
J. Biochem.
137
625-632
2005
Candida albicans (P10613), Candida albicans
Sheng, C.; Zhang, W.; Zhang, M.; Song, Y.; Ji, H.; Zhu, J.; Yao, J.; Yu, J.; Yang, S.; Zhou, Y.; Lu, J.
Homology modeling of lanosterol 14alpha-demethylase of Candida albicans and Aspergillus fumigatus and insights into the enzyme-substrate Interactions
J. Biomol. Struct. Dyn.
22
91-99
2004
Aspergillus fumigatus, Candida albicans
Cools, H.J.; Fraaije, B.A.; Kim, S.H.; Lucas, J.A.
Impact of changes in the target P450 CYP51 enzyme associated with altered triazole-sensitivity in fungal pathogens of cereal crops
Biochem. Soc. Trans.
34
1219-1222
2006
Candida albicans, Oculimacula yallundae, Zymoseptoria tritici, Blumeria graminis, Oculimacula acuformis
Lepesheva, G.I.; Waterman, M.R.
Sterol 14alpha-demethylase cytochrome P 450 (CYP51), a P450 in all biological kingdoms
Biochim. Biophys. Acta
1770
467-477
2007
Candida albicans, Homo sapiens, Methylococcus capsulatus, Mycobacterium tuberculosis, Mycolicibacterium smegmatis, Rattus norvegicus, Saccharomyces cerevisiae, Sorghum bicolor, Trypanosoma brucei, Trypanosoma cruzi, Ustilago maydis
Zhu, J.; Lu, J.; Zhou, Y.; Li, Y.; Cheng, J.; Zheng, C.
Design, synthesis, and antifungal activities in vitro of novel tetrahydroisoquinoline compounds based on the structure of lanosterol 14alpha-demethylase (CYP51) of fungi
Bioorg. Med. Chem. Lett.
16
5285-5289
2006
Aspergillus fumigatus, Candida albicans, Candida parapsilosis, Cryptococcus neoformans, Trichophyton rubrum, Microsporum canis
Sun, Q.Y.; Xu, J.M.; Cao, Y.B.; Zhang, W.N.; Wu, Q.Y.; Zhang, D.Z.; Zhang, J.; Zhao, H.Q.; Jiang, Y.Y.
Synthesis of novel triazole derivatives as inhibitors of cytochrome P450 14alpha-demethylase (CYP51)
Eur. J. Med. Chem.
20
1-8
2007
Aspergillus fumigatus, Candida albicans, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans, Nannizzia gypsea, Trichophyton rubrum, Fonsecaea compacta
Troesken, E.R.; Adamska, M.; Arand, M.; Zarn, J.A.; Patten, C.; Voelkel, W.; Lutz, W.K.
Comparison of lanosterol-14 alpha-demethylase (CYP51) of human and Candida albicans for inhibition by different antifungal azoles
Toxicology
228
24-32
2006
Candida albicans, Homo sapiens
Chen, S.H.; Sheng, C.Q.; Xu, X.H.; Jiang, Y.Y.; Zhang, W.N.; He, C.
Identification of Y118 amino acid residue in Candida albicans sterol 14alpha-demethylase associated with the enzyme activity and selective antifungal activity of azole analogues
Biol. Pharm. Bull.
30
1246-1253
2007
Candida albicans
Buckner, F.S.
Sterol 14-demethylase inhibitors for Trypanosoma cruzi infections
Adv. Exp. Med. Biol.
625
61-80
2008
Candida albicans, Homo sapiens, Mycobacterium tuberculosis, Trypanosoma brucei, Trypanosoma cruzi (Q7Z1V1), Trypanosoma cruzi
Chai, X.; Zhang, J.; Hu, H.; Yu, S.; Sun, Q.; Dan, Z.; Jiang, Y.; Wu, Q.
Design, synthesis, and biological evaluation of novel triazole derivatives as inhibitors of cytochrome P450 14alpha-demethylase
Eur. J. Med. Chem.
44
1913-1920
2009
Aspergillus fumigatus, Candida albicans, Pichia kudriavzevii, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans, Nannizzia gypsea, Trichophyton rubrum, Candida albicans ATCC 7661
Park, H.G.; Lee, I.S.; Chun, Y.J.; Yun, C.H.; Johnston, J.B.; Montellano, P.R.; Kim, D.
Heterologous expression and characterization of the sterol 14alpha-demethylase CYP51F1 from Candida albicans
Arch. Biochem. Biophys.
509
9-15
2011
Candida albicans (P10613), Candida albicans, Candida albicans ATCC MYA-2876 (P10613)
Alvarez-Rueda, N.; Fleury, A.; Morio, F.; Pagniez, F.; Gastinel, L.; Le Pape, P.
Amino acid substitutions at the major insertion loop of Candida albicans sterol 14alpha-demethylase are involved in fluconazole resistance
PLoS ONE
6
e21239
2011
Candida albicans
Hargrove, T.Y.; Friggeri, L.; Wawrzak, Z.; Qi, A.; Hoekstra, W.J.; Schotzinger, R.J.; York, J.D.; Guengerich, F.P.; Lepesheva, G.I.
Structural analyses of Candida albicans sterol 14alpha-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis
J. Biol. Chem.
292
6728-6743
2017
Candida albicans (Q9P4W0), Candida albicans
EXTERNAL LINKS (specific for EC-Number 1.14.14.154)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
