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

Škerlová, Jana ; Lindström, Helena ; Gonis, Elodie ; Sjödin, Birgitta ; Neiers, Fabrice ; Stenmark, Pål LU orcid and Mannervik, Bengt (2020) In FEBS Letters 594(7). p.1187-1195
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... (More)

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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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
FEBS Letters
volume
594
issue
7
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • pmid:31845319
  • scopus:85078306802
ISSN
1873-3468
DOI
10.1002/1873-3468.13718
language
English
LU publication?
yes
additional info
© 2019 Federation of European Biochemical Societies.
id
5dd260d7-af88-433d-ae10-39d2b6bd7aa9
date added to LUP
2019-12-18 22:08:13
date last changed
2023-03-23 23:09:02
@article{5dd260d7-af88-433d-ae10-39d2b6bd7aa9,
  abstract     = {{<p>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.</p>}},
  author       = {{Škerlová, Jana and Lindström, Helena and Gonis, Elodie and Sjödin, Birgitta and Neiers, Fabrice and Stenmark, Pål and Mannervik, Bengt}},
  issn         = {{1873-3468}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1187--1195}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{FEBS Letters}},
  title        = {{Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis}},
  url          = {{http://dx.doi.org/10.1002/1873-3468.13718}},
  doi          = {{10.1002/1873-3468.13718}},
  volume       = {{594}},
  year         = {{2020}},
}