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Literature summary for 1.1.1.62 extracted from

  • Nashev, L.; Atanasov, A.; Baker, M.; Odermatt, A.
    Cysteine-10 on 17beta-hydroxysteroid dehydrogenase 1 has stabilizing interactions in the cofactor binding region and renders sensitivity to sulfhydryl modifying chemicals (2013), Int. J. Cell Biol., 2013, 769536.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
diagnostics 17beta-HSD1 is highly expressed in breast and ovary tissues and represents a prognostic marker for the tumor progression and survival of patients with breast cancer and other estrogen-dependent tumors Homo sapiens
drug development the enzyme is considered a promising drug target against estrogen-dependent cancers Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene HSD17B1, sequence comparisons, recombinant expression in HEK-293 cells Homo sapiens
HSD17B1, recombinant expression in HEK-293 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
C10S site-directed mutagenesis, substitution of Cys10 with Ser results in a decreased protein half-life, without significantly altering kinetic properties. Mutant Cys10Ser shows approximately 50% lower activity compared to the wild-type. Mutating Cys10 to Ser does not lead to significant changes in contacts between Ser10 and Ile7, Gly9 and Ala34. But all three contacts between Ser10 and Gly15 are shorter than between Cys10 and Gly15, and Gly15 is more distant from a phosphate oxygen on NADP+ Homo sapiens
C10S site-directed mutagenesis, the Cys10Ser mutant 17beta-HSD1 is partially protected from inhibition by NEM and dithiocarbamates. Mutating Cys10 to Ser does not lead to significant changes in contacts between Ser10 and Ile7, Gly9 and Ala34, but all three contacts between Ser10 and Gly15 are shorter than between Cys10 and Gly15, and Gly15 is more distant from a phosphate oxygen on NADP+ Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Disulfiram irreversible inhibition Homo sapiens
Dithiocarbamate irreversible inhibition of 17beta-HSD1, preincubation with NADPH protects from inhibition Homo sapiens
maneb irreversible inhibition Homo sapiens
additional information the enzyme shows sensitivity towards sulfhydryl modifying chemicals. 17beta-HSD1 is irreversibly inhibited by the sulfhydrylmodifying agents N-ethylmaleimide and dithiocarbamates. Preincubation with increasing concentrations of NADPH protects 17beta-HSD1 from inhibition by these chemicals Homo sapiens
N-ethylmaleimide irreversible inhibition; irreversible inhibition of 17beta-HSD1, preincubation with NADPH protects from inhibition Homo sapiens
thiram irreversible inhibition Homo sapiens
zineb irreversible inhibition Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
additional information kinetics of wild-type and mutant enzymes, overview Homo sapiens
0.000043
-
estrone pH 7.4, 37°C, recombinant wild-type enzyme Homo sapiens
0.000065
-
estrone pH 7.4, 37°C, recombinant mutant C10S Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
17beta-estradiol + NAD(P)+ Homo sapiens
-
estrone + NAD(P)H + H+
-
r
estrone + NADPH + H+ Homo sapiens
-
17beta-estradiol + NADP+
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P14061
-
-

Source Tissue

Source Tissue Comment Organism Textmining
breast
-
Homo sapiens
-
breast cancer cell
-
Homo sapiens
-
additional information 17beta-HSD1 is highly expressed in breast and ovary tissues and represents a prognostic marker for the tumor progression and survival of patients with breast cancer and other estrogen-dependent tumors Homo sapiens
-
ovary
-
Homo sapiens
-
ovary cancer cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
17beta-estradiol + NAD(P)+
-
Homo sapiens estrone + NAD(P)H + H+
-
r
estrone + NADPH + H+
-
Homo sapiens 17beta-estradiol + NADP+
-
?

Subunits

Subunits Comment Organism
More enzyme three-dimensional structural modeling, overview Homo sapiens

Synonyms

Synonyms Comment Organism
17beta-HSD1
-
Homo sapiens
17beta-hydroxysteroid dehydrogenase 1
-
Homo sapiens
HSD17B1
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
assay at Homo sapiens
7.5
-
assay at Homo sapiens

Cofactor

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

General Information

General Information Comment Organism
evolution 17beta-HSD1 belongs to the short-chain dehydrogenase/reductase (SDR) family and contains the conserved Rossmann-fold for nucleotide binding, the catalytic triad with residues Ser142, Tyr155, and Lys159 and a dimerization region. Residue Cys10 is highly conserved among species, including rodents and zebrafish, suggesting a role for this residue in the stability and/or function of the protein. The cysteine residue at this position is conserved in all members of the SDR9C family, except for 17beta-HSD2, which has a cysteine residue downstream by two positions Homo sapiens
malfunction substitution of Cys10 with Ser in the enzyme results in a decreased protein half-life, without significantly altering kinetic properties Homo sapiens
additional information Lys149 is a critical residue for the discrimination between C-18 and C-19 steroid substrate. Analysis of the role of Cys10 for 17beta-HSD1 function, overview Homo sapiens
additional information role of a cysteine residue, Cys10 in the Rossmann-fold NADPH binding region, for 17beta-HSD1 function, important interactions of Cys10 with residues involved in the stabilization of amino acids of the NADPH binding pocket, three-dimensional enzyme structure modeling, overview Homo sapiens