Marmoset glutathione transferases with ketosteroid isomerase activity

• 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 (Delta(5)-AD) of 62.1 +/- 1.8 mu mol min(-1) mg(-1), and a k(cat) value of 261 +/- 49 s(-1). The second ketostemid isomerase CjaGST A1-1 has a 30-fold lower specific activity with Delta(5)-AD and a 37-fold lower k(cat) 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 mu M) and ethacrynic acid (IC50 =3.3 +/- 0.2 mu M) were found to be potent inhibitors of CjaGST A3-3, as previously demonstrated with the human and equine orthologs.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

5-Androsten-3

17-dione

5-Pregnen-3

20-dione

CjaGST A3-3

CjaGST A1-1

Alpha glutathione transferase

Steroid hormone synthesis

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)