BRENDA - Enzyme Database
show all sequences of 1.14.13.70

Structural analyses of Candida albicans sterol 14alpha-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

Hargrove, T.Y.; Friggeri, L.; Wawrzak, Z.; Qi, A.; Hoekstra, W.J.; Schotzinger, R.J.; York, J.D.; Guengerich, F.P.; Lepesheva, G.I.; J. Biol. Chem. 292, 6728-6743 (2017)

Data extracted from this reference:

Cloned(Commentary)
Cloned (Commentary)
Organism
expression in Escherichia coli
Candida albicans
Crystallization (Commentary)
Crystallization (Commentary)
Organism
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
Candida albicans
Inhibitors
Inhibitors
Commentary
Organism
Structure
(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
Candida albicans
clotrimazole
78% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
fluconazole
54% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
itraconazole
91% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
ketoconazole
85% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
miconazole
79% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
posaconazole
98% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
voriconazole
84% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
KM Value [mM]
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0063
-
lanosterol
pH and temperature not specified in the publication
Candida albicans
Organism
Organism
UniProt
Commentary
Textmining
Candida albicans
Q9P4W0
-
-
Purification (Commentary)
Purification (Commentary)
Organism
-
Candida albicans
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
Substrate Product ID
lanosterol + NADPH + H+ + O2
-
745378
Candida albicans
?
-
-
-
?
Synonyms
Synonyms
Commentary
Organism
CYP51
-
Candida albicans
Turnover Number [1/s]
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.55
-
lanosterol
pH and temperature not specified in the publication
Candida albicans
Cloned(Commentary) (protein specific)
Commentary
Organism
expression in Escherichia coli
Candida albicans
Crystallization (Commentary) (protein specific)
Crystallization
Organism
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
Candida albicans
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
(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
Candida albicans
clotrimazole
78% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
fluconazole
54% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
itraconazole
91% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
ketoconazole
85% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
miconazole
79% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
posaconazole
98% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
voriconazole
84% inhibition, molar ratio of enzyme/inhibitor/lanosterol was 1:2:50
Candida albicans
KM Value [mM] (protein specific)
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
0.0063
-
lanosterol
pH and temperature not specified in the publication
Candida albicans
Purification (Commentary) (protein specific)
Commentary
Organism
-
Candida albicans
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
ID
lanosterol + NADPH + H+ + O2
-
745378
Candida albicans
?
-
-
-
?
Turnover Number [1/s] (protein specific)
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
0.55
-
lanosterol
pH and temperature not specified in the publication
Candida albicans
KCat/KM [mM/s]
kcat/KM Value [1/mMs-1]
kcat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
87.3
-
lanosterol
pH and temperature not specified in the publication
Candida albicans
KCat/KM [mM/s] (protein specific)
KCat/KM Value [1/mMs-1]
KCat/KM Value Maximum [1/mMs-1]
Substrate
Commentary
Organism
Structure
87.3
-
lanosterol
pH and temperature not specified in the publication
Candida albicans
Other publictions for EC 1.14.13.70
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Synonyms
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
744274
Park
Nitric oxide stimulates cellu ...
Homo sapiens
Biochem. J.
474
3241-3252
2017
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
744843
Emami
An overview of azoles targeti ...
Leishmania major, Leishmania mexicana, Leishmania infantum
Eur. J. Med. Chem.
135
241-259
2017
-
6
-
-
-
-
39
-
-
-
-
-
-
3
-
-
-
-
-
6
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
4
-
6
-
-
-
-
-
4
39
-
-
-
-
-
-
-
-
-
-
-
6
-
-
6
-
-
-
-
-
-
-
-
-
-
6
6
-
-
-
744860
Borcea
-
Synthesis and molecular docki ...
Candida albicans SC5314
Farmacia
65
683-689
2017
-
-
-
-
-
-
10
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
10
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
745117
Stana
Design, synthesis and antifun ...
Candida albicans SC5314
Int. J. Mol. Sci.
18
E177
2017
-
2
-
-
-
-
6
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
2
-
-
-
745378
Hargrove
Structural analyses of Candid ...
Candida albicans
J. Biol. Chem.
292
6728-6743
2017
-
-
1
1
-
-
8
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
1
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
1
-
1
-
-
-
8
-
1
-
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
-
-
-
1
1
745682
Alvarez-Rueda
The amino acid substitution N ...
Candida albicans
Med. Mycol.
54
764-775
2016
-
-
1
-
1
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
1
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
746216
Tyndall
Structural and functional elu ...
Saccharomyces cerevisiae, Saccharomyces cerevisiae YJM789
PLoS ONE
11
e0167485
2016
-
-
1
1
2
-
7
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
1
2
-
-
7
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
746454
Warrilow
Azole antifungal sensitivity ...
Malassezia globosa, Malassezia globosa CBS 7966
Sci. Rep.
6
27690
2016
-
-
1
-
-
-
4
3
-
-
-
-
-
2
-
-
1
-
-
-
-
-
5
-
1
1
-
-
3
1
-
-
-
-
-
4
-
-
1
-
-
-
-
4
4
-
3
-
-
-
-
-
-
-
1
-
-
-
-
5
-
1
-
-
3
1
-
-
-
-
-
-
-
3
3
744385
Morrison
Identification, modeling and ...
Danio rerio
Biochim. Biophys. Acta
1840
1825-1836
2014
-
-
1
-
-
-
2
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
745522
Friggeri
Structural basis for rational ...
Trypanosoma cruzi, Trypanosoma cruzi CL Brener
J. Med. Chem.
57
6704-6717
2014
-
2
1
1
-
-
2
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
2
-
1
-
-
-
-
-
-
-
-
-
-
-
-
2
1
-
1
-
-
-
2
-
-
-
-
-
-
-
-
-
1
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-