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 (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 | 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 | 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 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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P14061 | - |
- |
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 | 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 | Comment | Organism |
---|---|---|
More | enzyme three-dimensional structural modeling, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
17beta-HSD1 | - |
Homo sapiens |
17beta-hydroxysteroid dehydrogenase 1 | - |
Homo sapiens |
HSD17B1 | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
7.5 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens | |
NADH | - |
Homo sapiens | |
NADP+ | - |
Homo sapiens | |
NADPH | - |
Homo sapiens |
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 |