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Literature summary for 5.3.3.1 extracted from

  • Pletnev, V.Z.; Thomas, J.L.; Rhaney, F.L.; Holt, L.S.; Scaccia, L.A.; Umland, T.C.; Duax, W.L.
    Rational proteomics V: structure-based mutagenesis has revealed key residues responsible for substrate recognition and catalysis by the dehydrogenase and isomerase activities in human 3beta-hydroxysteroid dehydrogenase/isomerase type 1 (2006), J. Steroid Biochem. Mol. Biol., 101, 50-60.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 5.3.3.1

Activating Compound

Activating Compound Comment Organism Structure
NADH the cofactor acts as an allosteric activator Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of type 1 isozyme, wild-type and mutant enzymes, in Spodoptera frugiperda Sf9 cells via baculovirus infection Homo sapiens

Protein Variants

Protein Variants Comment Organism
E126L site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
H156Y site-directed mutagenesis, leads to destabilization of interactions at the dimer interface and a dramatic increase in the substrate Km and inhibitor Ki values of 3beta-HSD isozyme 1 to equal those measured for 3beta-HSD isozyme 2 Homo sapiens
H232A site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
K158Q site-directed mutagenesis, results in the complete loss of dehydrogenase activity and a reduction in isomerase activity, probably due to partial destabilization of cofactor binding, in which the catalytic triad is actively involved, and associated substrate binding Homo sapiens
N100A site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
N100S site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
N323L site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
Q105M site-directed mutagenesis, leads to destabilization of interactions at the dimer interface and a dramatic increase in the substrate Km and inhibitor Ki values of 3beta-HSD isozyme 1 to equal those measured for 3beta-HSD isozyme 2 Homo sapiens
S124A site-directed mutagenesis, results in the complete loss of dehydrogenase activity and a reduction in isomerase activity, probably due to partial destabilization of cofactor binding, in which the catalytic triad is actively involved, and associated substrate binding Homo sapiens
S322A site-directed mutagenesis, altered kinetics compared to the wild-type enzyme Homo sapiens
Y154F site-directed mutagenesis, results in the complete loss of dehydrogenase activity and a reduction in isomerase activity, probably due to partial destabilization of cofactor binding, in which the catalytic triad is actively involved, and associated substrate binding 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 Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens the bifunctional enzyme possesses 3beta-hydroxysteroid dehydrogenase activity, EC 1.1.1.51, and steroid DELTA-isomerase activity, the enzyme is a key steroidogenic enzyme that catalyzes the first step of the multienzyme pathway conversion of circulating dehydroepiandrosterone and pregnenolone to active steroid hormones ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P14060 isozyme type 1; isozyme type 1
-
Homo sapiens P26439 isozyme type 2; isozyme type 2
-

Purification (Commentary)

Purification (Comment) Organism
recombinant type 1 isozyme, wild-type and mutant enzymes, from Spodoptera frugiperda Sf9 cells Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
adrenal gland type 2 isozyme Homo sapiens
-
mammary gland type 1 isozyme Homo sapiens
-
ovary type 2 isozyme Homo sapiens
-
placenta type 1 isozyme Homo sapiens
-
prostate type 1 isozyme Homo sapiens
-
testis type 2 isozyme Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5-Androstene-3,17-dione
-
 Homo sapiens 4-Androstene-3,17-dione
-
 ?
additional information the bifunctional enzyme possesses 3beta-hydroxysteroid dehydrogenase activity, EC 1.1.1.51, and steroid DELTA-isomerase activity, the enzyme is a key steroidogenic enzyme that catalyzes the first step of the multienzyme pathway conversion of circulating dehydroepiandrosterone and pregnenolone to active steroid hormones Homo sapiens ?
-
 ?
additional information structure-function relations, analysis of three dimensional model of a ternary complex of human 3beta-HSD type 1 with an NAD+ cofactor and androstenedione product, reaction of EC 1.1.1.51, to elucidate the key substrate binding residues in the active site as well as the basis for dual function of the 3beta-HSD_1 enzyme, Asn100 and Glu126 residues are key residues that participate in the dehydrogenase and isomerization reactions, respectively, isomerase substrate binding structure, overview Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
dimer active enzyme, interface is composed of two pairs of helices related by a 2fold symmetry axis, involved residues, overview Homo sapiens

Synonyms

Synonyms Comment Organism
3beta-HSD
-
 Homo sapiens
3beta-hydroxysteroid dehydrogenase/isomerase type 1
-
 Homo sapiens
3beta-hydroxysteroid dehydrogenase/isomerase type 2
-
 Homo sapiens
More the enzyme is a member of the short chain dehydrogenase/reductase family, cf. EC 1.1.1.51 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
27
-
 assay at Homo sapiens

pH Optimum

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

Cofactor

Cofactor Comment Organism Structure
NADH the cofactor acts as an allosteric activator Homo sapiens