Marmoset glutathione transferases with ketosteroid isomerase activity
| Autor: | Julia Sawmi, Bengt Mannervik, Aram Ismail |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Isomerase activity
4-androsten-3 17-dione (Δ4-AD) QH301-705.5 CjaGST A1-1 medicine.medical_treatment Biophysics 5-Pregnen-3 20-dione QD415-436 5-androsten-3 17-dione (Δ5-AD) Isomerase phenethyl isothiocyanate (PEITC) Biochemistry Steroid hormone synthesis Steroid 5-Androsten-3 17-dione chemistry.chemical_compound Ketosteroid biology.animal Glutathione (GSH) medicine Enzyme kinetics Biology (General) allyl isothiocyanate (AITC) 1-chloro-2 4-dinitrobenzene (CDNB) chemistry.chemical_classification Glutathione transferase (GST) 5-pregnen-3 20-dione (Δ5-PD) biology Marmoset Enzyme chemistry Alpha glutathione transferase CjaGST A3-3 Specific activity Research Article SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) |
| Zdroj: | Biochemistry and Biophysics Reports Biochemistry and Biophysics Reports, Vol 27, Iss, Pp 101078-(2021) |
| ISSN: | 2405-5808 |
| DOI: | 10.1016/j.bbrep.2021.101078 |
| Popis: | The common marmoset Callithrix jacchus encodes two glutathione transferase (GST) enzymes with ketosteroid double-bond isomerase activity. The most active enzyme is CjaGST A3-3 showing a specific activity with 5-androsten-3,17-dione (Δ5-AD) of 62.1 ± 1.8 μmol min-1 mg-1, and a kcat value of 261 ± 49 s-1. The second ketosteroid isomerase CjaGST A1-1 has a 30-fold lower specific activity with Δ5-AD and a 37-fold lower kcat value. Thus, the marmoset CjaGST A3-3 would be the main contributor to the biosynthesis of the steroid hormones testosterone and progesterone, like the human ortholog HsaGST A3-3. Two residues differ in the H-site of the 91.4% sequence identical CjaGST A1-1 and CjaGST A3-3, and modeling of the structures suggests that the bulky phenyl ring of Phe111 in CjaGST A1-1 causes steric hindrance in the binding of the steroid substrate. Tributyltin acetate (IC50=0.16 ± 0.004 μM) and ethacrynic acid (IC50=3.3 ± 0.2 μM) were found to be potent inhibitors of CjaGST A3-3, as previously demonstrated with the human and equine orthologs. Highlights • Marmoset glutathione transferase A3-3 displays potent ketosteroid isomerase activity. • Marmoset glutathione transferase A1-1 shows weak ketosteroid isomerase activity. • A model of marmoset A1-1 suggests active-site Phe to interfere with steroid binding. • Common marmoset monkey – a possible model animal for steroid biosynthesis research. |
| Databáze: | OpenAIRE |
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