Literature summary for 1.1.1.64 extracted from

Amano, Y.; Yamaguchi, T.; Niimi, T.; Sakashita, H.
Structures of complexes of type 5 17beta-hydroxysteroid dehydrogenase with structurally diverse inhibitors: insights into the conformational changes upon inhibitor binding (2015), Acta Crystallogr. Sect. D, 71, 918-927.

Application

Application	Comment	Organism
drug development	testosterone is converted to 5alpha-dihydrotestosterone, which is present at high concentrations in patients with castration resistant prostate cancer (CRPC). Inhibition of 17beta-HSD5 is therefore considered to be a promising therapy for treating CRPC. High-throughput inhibitor screening, overview	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in ternary complex with NADP+ and one inhibitor, from inhibitors 1-6, 15 mg/ml protein in 10 mM potassium phosphate pH 7.4, 500 mM NaCl, 1 mM ethylenediaminetetraacetic acid, 1 mM dithiothreitol is mixed with crystallization solution containing 0.1 M sodium citrate, pH 5.5, 0.4 M ammonium acetate, 2.5% v/v 2-methyl-2,4-pentanediol, 22-30% w/v PEG 4000 for inhibitors 1-4, and containing 0.1 M HEPES pH 6.5, 0.2 M ammonium dihydrogen phosphate, 20-25% w/v PEG 3350 for inhibitors 5 and 6, X-ray diffraction structure determination analysis at 1.55-2.81 A resolution, modelling	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme in ternary complex with NADP+ and one inhibitor, from inhibitors 1-6, 15 mg/ml protein in 10 mM potassium phosphate pH 7.4, 500 mM NaCl, 1 mM ethylenediaminetetraacetic acid, 1 mM dithiothreitol is mixed with crystallization solution containing 0.1 M sodium citrate, pH 5.5, 0.4 M ammonium acetate, 2.5% v/v 2-methyl-2,4-pentanediol, 22-30% w/v PEG 4000 for inhibitors 1-4, and containing 0.1 M HEPES pH 6.5, 0.2 M ammonium dihydrogen phosphate, 20-25% w/v PEG 3350 for inhibitors 5 and 6, X-ray diffraction structure determination analysis at 1.55-2.81 A resolution, modelling

Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone	crystal structure analysis of enzyme-inhibitor complex	Homo sapiens
(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone	crystal structure analysis of enzyme-inhibitor complex	Homo sapiens
3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one	crystal structure analysis of enzyme-inhibitor complex	Homo sapiens
4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide	crystal structure analysis of enzyme-inhibitor complex	Homo sapiens
4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol	crystal structure analysis of enzyme-inhibitor complex	Homo sapiens
5-(benzenesulfonyl)-2-nitrophenol	crystal structure analysis of enzyme-inhibitor complex	Homo sapiens
additional information	crystal structures of complexes of 17beta-HSD5 with structurally diverse inhibitors derived from high-throughput inhibitor screening, overview. Analysis of interactions between 17beta-HSD5 and inhibitors at the atomic level which enable structure-based drug design for anti-CRPC therapy	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
testosterone + NADP+	Homo sapiens	-	androstenedione + NADPH + H+	-	r

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P42330	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity and anion exchange chromatography, gel fitration, and ultrafiltration	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
prostate	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
testosterone + NADP+	-	Homo sapiens	androstenedione + NADPH + H+	-	r

Synonyms

Synonyms	Comment	Organism
17beta-HSD5	-	Homo sapiens
AKR1C3	-	Homo sapiens
type 5 17beta-hydroxysteroid dehydrogenase	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
22	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
6	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
NADP+	-	Homo sapiens
NADPH	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor
0.000037	-	pH 6.0, 22°C	Homo sapiens	(5-methyl-1H-indol-2-yl)(4-propylpiperidin-1-yl)methanone
0.00029	-	pH 6.0, 22°C	Homo sapiens	5-(benzenesulfonyl)-2-nitrophenol
0.00049	-	pH 6.0, 22°C	Homo sapiens	4-nitro-2-([4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl)phenol
0.0026	-	pH 6.0, 22°C	Homo sapiens	4-chloro-N-[(4-chlorophenyl)methyl]-5-nitro-1H-pyrazole-3-carboxamide
0.0028	-	pH 6.0, 22°C	Homo sapiens	(3,6-dihydropyridin-1(2H)-yl)(1H-indol-2-yl)methanone
0.0029	-	pH 6.0, 22°C	Homo sapiens	3-pentyl-2-[[(pyridin-2-yl)methyl]sulfanyl]-7-(pyrrolidine-1-carbonyl)quinazolin-4(3H)-one

General Information

General Information	Comment	Organism
evolution	the enzyme belongs to the AKR1C subfamily, the members of which catalyze the reduction of ketosteroids and ketoprostaglandins	Homo sapiens