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

Jana Škerlová; Helena Lindström; Elodie Gonis; Birgitta Sjödin; Fabrice Neiers; Pål Stenmark; Bengt Mannervik

doi:10.1002/1873-3468.13718

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

Jana Škerlová, Helena Lindström, Elodie Gonis, Birgitta Sjödin, Fabrice Neiers, Pål Stenmark, Bengt Mannervik

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Abstract

Ecdysteroids are critically important for 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 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 glutathione 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.

Original language	English
Pages (from-to)	1187-1195
Number of pages	9
Journal	FEBS Letters
Volume	594
Issue number	7
Early online date	2019 Dec 16
DOIs	https://doi.org/10.1002/1873-3468.13718
Publication status	Published - 2020 Apr

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Medicinal Chemistry

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title = "Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis",

abstract = "Ecdysteroids are critically important for 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 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 glutathione 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.",

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AU - Škerlová, Jana

AU - Lindström, Helena

AU - Gonis, Elodie

AU - Sjödin, Birgitta

AU - Neiers, Fabrice

AU - Stenmark, Pål

AU - Mannervik, Bengt

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AB - Ecdysteroids are critically important for 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 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 glutathione 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.

U2 - 10.1002/1873-3468.13718

DO - 10.1002/1873-3468.13718

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SN - 1873-3468

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JF - FEBS Letters

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ER -

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

Abstract

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