Molecular cloning and amino acid sequence of the porcine 17β‐estradiol dehydrogenase

Leenders, Frauke; Adamski, Jerzy; Husen, Bettina; Thole, Hubert; Jungblut, P. W.

doi:10.1111/j.1432-1033.1994.tb18860.x

Cited by 91 publications

(62 citation statements)

References 19 publications

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“…Peroxisomal ␤-oxidation enzymes are peroxisome matrix proteins that harbor PTS1 or PTS2 sequences. Three ␤-oxidation PTS1 enzymes, acyl-CoA oxidase (AOx) and D-bifunctional protein (DBP)/multifunctional enzyme 2/Hsd17b4 (hereafter termed DBP), which catalyze the oxidation of fatty acyl-CoA and the subsequent sequential hydration and dehydrogenation reactions, respectively (19,20), and sterol carrier protein x (SCPx), which catalyzes the last acetyl-CoA-cleaving step, were recently suggested to undergo proteolytic processing by the peroxisomal PTS1-type protease trypsin domain-containing 1 (Tysnd1) (21). Tysnd1 also cleaves the PTS2 presequence from peroxisomal 3-ketoacyl-CoA thiolase (TH), which catalyzes the last step of peroxisomal ␤-oxidation (21).…”

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confidence: 99%

Two Proteases, Trypsin Domain-containing 1 (Tysnd1) and Peroxisomal Lon Protease (PsLon), Cooperatively Regulate Fatty Acid β-Oxidation in Peroxisomal Matrix

Okumoto

Kametani

Fujiki

2011

Journal of Biological Chemistry

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Background: Tysnd1 and PsLon are newly identified peroxisomal matrix serine proteases. Results: Tysnd1 inactivates its protease activity by self-conversion of the 60-kDa form to 15-and 45-kDa chains that are then degraded by PsLon. Tysnd1 regulates the peroxisomal fatty acid ␤-oxidation pathway via proteolytic processing of ␤-oxidation enzymes. Conclusion: Tysnd1 and PsLon cooperatively regulate fatty acid ␤-oxidation in peroxisomal matrix. Significance: The data shed light on how enzyme turnover is regulated inside peroxisomes.

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Two Proteases, Trypsin Domain-containing 1 (Tysnd1) and Peroxisomal Lon Protease (PsLon), Cooperatively Regulate Fatty Acid β-Oxidation in Peroxisomal Matrix

Okumoto

Kametani

Fujiki

2011

Journal of Biological Chemistry

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“…In addition to displaying varied tissue distribution and diverse subcellular locations as well as a broad ligand spectrum, SCP2 domains are found in variable molecular contexts [1]. For example mammalian 58 kDa SCPx consists of SCP2 fused C-terminal to 3-oxoacyl-CoA thiolase (reviewed in [1]) while the 80 kDa multi-functional enzyme MFE-2 comprises an N-terminal (3R)-hydroxyacyl-CoA dehydrogenase, a 2-enoyl-CoA hydratase 2 domain and a C-terminal SCP2-like domain [6]. Further to this, different isoforms of the same gene product can be found in a single cell-the SCPx gene can produce an alternate transcript encoding 15 kDa preSCP2 [1,7], identical to the C-terminal domain of SCPx.…”

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Investigation of the ligand spectrum of human sterol carrier protein 2 using a direct mass spectrometry assay

Stanley

Versluis

Schultz

et al. 2007

Archives of Biochemistry and Biophysics

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Sterol carrier protein 2 (SCP2) has been investigated by nearly native electrospray ionisation mass spectrometry in the presence of long chain fatty acyl CoAs (LCFA-CoAs) and carnitine derivatives of equivalent fatty acid chain length (LCFA-carnitines). Four SCP2 constructs were compared to examine the influence of the N-terminal presequence and the C-terminal peroxisomal targeting signal on ligand binding. Removal of N-or C-terminal residues did not influence ligand binding. The observation that LCFA-CoAs are high affinity ligands for SCP2 was confirmed, while LCFA-carnitines were demonstrated for the first time not to interact with SCP2. LCFACoAs formed non-covalent complexes with SCP2 of 2:1 and 1:1 stoichiometry, which could be dissociated by elevating the energy of the ions upon entrance to the mass spectrometer. A fluorescence-competition assay using Nile Red butyric acid confirmed the mass spectrometric observations in solution. The physiological significance of the lack of LCFA-carnitine binding by SCP2 is discussed.

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“…At that time, Ke 6 was most similar to bacterial oxidoreductases with no close similarity to any mammalian oxidoreductase in the data base, leaving the exact function of Ke 6 unknown. Recently, we searched the data base again with Ke 6 and found it is similar to 17␤HSD4 (9). This prompted us to examine Ke 6 for 17␤HSD activity with various androgen and estrogen substrates.…”

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confidence: 99%

Characterization of Ke 6, a New 17β-Hydroxysteroid Dehydrogenase, and Its Expression in Gonadal Tissues

Fomitcheva¹,

Baker²,

Anderson³

et al. 1998

Journal of Biological Chemistry

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The abnormal regulation of the Ke 6 gene has been linked to the development of recessive polycystic kidney disease in the mouse. In this report, we have shown that Ke 6 is a 17␤-hydroxysteroid dehydrogenase and can regulate the concentration of biologically active estrogens and androgens. The Ke 6 enzyme is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. We find that the Ke 6 gene is expressed within the ovaries and testes. The presence of Ke 6 protein within the cumulus cells surrounding the oocyte places it in a strategic location to control the level of steroids to which the egg is exposed. Previously, it had been shown that glucocorticoids can induce renal cysts in the neonatal rodent, only when given at a narrow time window of postnatal kidney development. We propose that the reduction in the level of Ke 6 enzyme, which occurs in the cpk, jck, and pcy mice, may lead to abnormal elevations in local level of sex steroids, which either directly or indirectly via abnormal glucocorticoid metabolism result in recessive renal cystic disease, a developmental disorder of the kidney.The Ke 6 gene, encoded within the major histocompatibility complex, has been intimately linked to the development of cysts in the kidney and liver of mice (1-6). The expression of the Ke 6 gene is severely down-regulated in all murine models of PKD 1 that have been examined to date: cpk, jck (1, 3) and pcy mice (2). The inhibition of the Ke 6 gene expression using antisense deoxyoligonucleotides in embryonic kidneys in organ cultures gives rise to numerous cysts against a background of normal nephrogenesis (5, 6). Importantly, the human Ke 6 gene is located on chromosome 6p21 (7) where the human autosomal recessive PKD mutation has been mapped (8) and therefore there is a possibility that the Ke 6 gene is the primary mutation in autosomal recessive PKD. The structure of the mouse Ke 6 gene (2), cDNA (1), and protein (4) has been extensively characterized in our laboratory.Our earlier data base searches with the Ke 6 sequence showed that it belongs to the short-chain dehydrogenase/reductase family (1). At that time, Ke 6 was most similar to bacterial oxidoreductases with no close similarity to any mammalian oxidoreductase in the data base, leaving the exact function of Ke 6 unknown. Recently, we searched the data base again with Ke 6 and found it is similar to 17␤HSD4 (9). This prompted us to examine Ke 6 for 17␤HSD activity with various androgen and estrogen substrates.As reported here, we find that Ke 6 protein is an NAD-dependent 17␤HSD, making it the seventh member of this class of enzyme. It efficiently catalyzes the oxidation of estradiol, testosterone, and dihydrotestosterone and also the reduction of estrone to form biologically active estradiol. The identification of the substrate of Ke 6 allows us to postulate that regulated sex steroid metabolism plays a crucial role in the development o...

show abstract

Molecular cloning and amino acid sequence of the porcine 17β‐estradiol dehydrogenase

Cited by 91 publications

References 19 publications

Two Proteases, Trypsin Domain-containing 1 (Tysnd1) and Peroxisomal Lon Protease (PsLon), Cooperatively Regulate Fatty Acid β-Oxidation in Peroxisomal Matrix

Two Proteases, Trypsin Domain-containing 1 (Tysnd1) and Peroxisomal Lon Protease (PsLon), Cooperatively Regulate Fatty Acid β-Oxidation in Peroxisomal Matrix

Investigation of the ligand spectrum of human sterol carrier protein 2 using a direct mass spectrometry assay

Characterization of Ke 6, a New 17β-Hydroxysteroid Dehydrogenase, and Its Expression in Gonadal Tissues

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