Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis

DOI: 10.1002/1873-3468.13718

Authors: Jana Skerlova (Stockholm University) , Helena Lindström (Stockholm University) , Elodie Gonis (University Bourgogne Franche‐Comté) , Birgitta Sjödin (Stockholm University) , Fabrice Neiers (University Bourgogne Franche‐Comté) , Pal Stenmark (Stockholm University) , Bengt Mannervik (Stockholm University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Febs Letters

State: Published (Approved)
Published: January 2020
Diamond Proposal Number(s): 21625

Abstract: Ecdysteroids are critically important for the formation of the insect exoskeleton. Cholesterol is a precursor of ecdysone and its active form 20‐hydroxyecdysone, but some steps in the ecdysteroid biosynthesis pathway remain unknown. An essential requirement of glutathione (GSH) transferase GSTE14 in ecdysteroid biosynthesis has been established in Drosophila melanogaster, but its function is entirely unknown. Here, we have determined the crystal structure of GSTE14 in complex with GSH and investigated the kinetic properties of GSTE14 with alternative substrates. GSTE14 has high‐ranking steroid double‐bond isomerase activity, albeit 50‐fold lower than the most efficient mammalian GSTs. Corresponding steroid isomerizations are unknown in insects, and their exact physiological role remains to be shown. Nonetheless, the essential enzyme GSTE14 is here demonstrated to be catalytically competent and have a steroid‐binding site.

Journal Keywords: Drosophila GSTE14; ecdysteroid; glutathione transferase; Noppera‐bo; steroid double‐bond isomerization

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I04-Macromolecular Crystallography

Added On: 29/01/2020 10:47

Documents:
-kerlov-_et_al-2020.pdf

Discipline Tags:

Biochemistry Catalysis Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)