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Literature summary for 1.1.1.149 extracted from

  • El-Kabbani, O.; Scammells, P.J.; Day, T.; Dhagat, U.; Endo, S.; Matsunaga, T.; Soda, M.; Hara, A.
    Structure-based optimization and biological evaluation of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) salicylic acid-based inhibitors (2010), Eur. J. Med. Chem., 45, 5309-5317.
    View publication on PubMed

Crystallization (Commentary)

Crystallization (Comment) Organism
mutant L308V in complex with the inhibitor 3,5-dichlorosalicylic acid, to 1.9 A resolution. The inhibitor molecule is anchored from its carboxylate group that forms hydrogen bonds with the catalytic residues His117 and Tyr55, while the hydroxyl group is hydrogen bonded to His222. Van der Waals contacts are present between the inhibitor and residues Leu54, Leu306, and Phe311. Unlike the WT enzyme, the side-chain of the mutated Val308 makes long contacts with the inhibitor, the closest point of contact being 3.9 A Homo sapiens

Protein Variants

Protein Variants Comment Organism
L308A mutation results in 473-fold and 27fold reductions in the inhibitory potencies of 3,5-dichlorosalicylic acid and 3-bromo-5-phenylsalicylic acid, respectively Homo sapiens
L308V crystallization data. Mutation results in 13-fold and 3fold reductions in the inhibitory potencies of 3,5-dichlorosalicylic acid and 3-bromo-5-phenylsalicylic acid, respectively Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
3,5-dichlorosalicylic acid
-
Homo sapiens
3-bromo-5-phenylsalicylic acid
-
Homo sapiens
3-chloro-5-phenylsalicylic acid
-
Homo sapiens
4'-butyl-5-chloro-4-hydroxybiphenyl-3-carboxylic acid 7fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2 Homo sapiens
5-chloro-4-hydroxy-3'-methylbiphenyl-3-carboxylic acid 13fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2 Homo sapiens
5-chloro-4-hydroxy-4'-methylbiphenyl-3-carboxylic acid 24fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2 Homo sapiens
5-chloro-4-hydroxybiphenyl-3-carboxylic acid 24fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2 Homo sapiens
5-fluoro-4-hydroxybiphenyl-3-carboxylic acid 1.2fold selectivity relative to 3alpha-hydroxysteroid dehydrogenase AKR1C2 Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q04828
-
-

Synonyms

Synonyms Comment Organism
AKR1C1 gen name Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00000086
-
5-chloro-4-hydroxybiphenyl-3-carboxylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.0000013
-
5-chloro-4-hydroxy-3'-methylbiphenyl-3-carboxylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.0000013
-
5-fluoro-4-hydroxybiphenyl-3-carboxylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.0000021
-
4'-butyl-5-chloro-4-hydroxybiphenyl-3-carboxylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.0000026
-
5-chloro-4-hydroxy-4'-methylbiphenyl-3-carboxylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.0000041
-
3-bromo-5-phenylsalicylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.0000059
-
3,5-dichlorosalicylic acid wild-type, 25°C, pH not specified in the publication Homo sapiens
0.000014
-
3-bromo-5-phenylsalicylic acid mutant L308V, 25°C, pH not specified in the publication Homo sapiens
0.000078
-
3,5-dichlorosalicylic acid mutant L308V, 25°C, pH not specified in the publication Homo sapiens
0.000113
-
3-bromo-5-phenylsalicylic acid mutant L308A, 25°C, pH not specified in the publication Homo sapiens
0.00279
-
3,5-dichlorosalicylic acid mutant L308A, 25°C, pH not specified in the publication Homo sapiens