6t2t

Crystal structure of Drosophila melanogaster glutathione S-transferase epsilon 14 in complex with glutathione and 2-methyl-2,4-pentanediolCrystal structure of Drosophila melanogaster glutathione S-transferase epsilon 14 in complex with glutathione and 2-methyl-2,4-pentanediol

Structural highlights

6t2t is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.3Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GSTEE_DROME Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles (PubMed:22082028). Essential for ecdysteroid biosynthesis (PubMed:25344753, PubMed:25300303). May be involved in detoxification (PubMed:22082028).^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis.,Skerlova J, Lindstrom H, Gonis E, Sjodin B, Neiers F, Stenmark P, Mannervik B FEBS Lett. 2019 Dec 16. doi: 10.1002/1873-3468.13718. PMID:31845319^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Saisawang C, Wongsantichon J, Ketterman AJ. A preliminary characterization of the cytosolic glutathione transferase proteome from Drosophila melanogaster. Biochem J. 2012 Feb 15;442(1):181-90. doi: 10.1042/BJ20111747. PMID:22082028 doi:http://dx.doi.org/10.1042/BJ20111747
↑ Enya S, Ameku T, Igarashi F, Iga M, Kataoka H, Shinoda T, Niwa R. A Halloween gene noppera-bo encodes a glutathione S-transferase essential for ecdysteroid biosynthesis via regulating the behaviour of cholesterol in Drosophila. Sci Rep. 2014 Oct 10;4:6586. doi: 10.1038/srep06586. PMID:25300303 doi:http://dx.doi.org/10.1038/srep06586
↑ Chanut-Delalande H, Hashimoto Y, Pelissier-Monier A, Spokony R, Dib A, Kondo T, Bohere J, Niimi K, Latapie Y, Inagaki S, Dubois L, Valenti P, Polesello C, Kobayashi S, Moussian B, White KP, Plaza S, Kageyama Y, Payre F. Pri peptides are mediators of ecdysone for the temporal control of development. Nat Cell Biol. 2014 Nov;16(11):1035-44. doi: 10.1038/ncb3052. Epub 2014 Oct 26. PMID:25344753 doi:http://dx.doi.org/10.1038/ncb3052
↑ Skerlova J, Lindstrom H, Gonis E, Sjodin B, Neiers F, Stenmark P, Mannervik B. Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis. FEBS Lett. 2019 Dec 16. doi: 10.1002/1873-3468.13718. PMID:31845319 doi:http://dx.doi.org/10.1002/1873-3468.13718

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OCA

[1] Saisawang C, Wongsantichon J, Ketterman AJ. A preliminary characterization of the cytosolic glutathione transferase proteome from Drosophila melanogaster. Biochem J. 2012 Feb 15;442(1):181-90. doi: 10.1042/BJ20111747. PMID:22082028 doi:http://dx.doi.org/10.1042/BJ20111747

[2] Enya S, Ameku T, Igarashi F, Iga M, Kataoka H, Shinoda T, Niwa R. A Halloween gene noppera-bo encodes a glutathione S-transferase essential for ecdysteroid biosynthesis via regulating the behaviour of cholesterol in Drosophila. Sci Rep. 2014 Oct 10;4:6586. doi: 10.1038/srep06586. PMID:25300303 doi:http://dx.doi.org/10.1038/srep06586

[3] Chanut-Delalande H, Hashimoto Y, Pelissier-Monier A, Spokony R, Dib A, Kondo T, Bohere J, Niimi K, Latapie Y, Inagaki S, Dubois L, Valenti P, Polesello C, Kobayashi S, Moussian B, White KP, Plaza S, Kageyama Y, Payre F. Pri peptides are mediators of ecdysone for the temporal control of development. Nat Cell Biol. 2014 Nov;16(11):1035-44. doi: 10.1038/ncb3052. Epub 2014 Oct 26. PMID:25344753 doi:http://dx.doi.org/10.1038/ncb3052

[4] Skerlova J, Lindstrom H, Gonis E, Sjodin B, Neiers F, Stenmark P, Mannervik B. Structure and steroid isomerase activity of Drosophila glutathione transferase E14 essential for ecdysteroid biosynthesis. FEBS Lett. 2019 Dec 16. doi: 10.1002/1873-3468.13718. PMID:31845319 doi:http://dx.doi.org/10.1002/1873-3468.13718

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