6ker

Crystal structure of D113A mutant of Drosophila melanogaster Noppera-bo, glutathione S-transferase epsilon 14 (DmGSTE14), in glutathione-bound form

spinqualitylabelsall models 6ker, resolution 1.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ker is a 2 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 1.84Å Ligands: GSH 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). Publication Abstract from PubMed Ecdysteroids are the principal steroid hormones essential for insect development and physiology. In the last 18 years, several enzymes responsible for ecdysteroid biosynthesis encoded by Halloween genes were identified and genetically and biochemically characterized. However, the tertiary structures of these proteins have not yet been characterized. Here, we report the results of an integrated series of in silico, in vitro, and in vivo analyses of the Halloween GST protein Noppera-bo (Nobo). We determined crystal structures of Drosophila melanogaster Nobo (DmNobo) complexed with glutathione and 17beta-estradiol, a DmNobo inhibitor. 17beta-Estradiol almost fully occupied the putative ligand-binding pocket and a prominent hydrogen bond formed between 17beta-estradiol and Asp-113 of DmNobo. We found that Asp-113 is essential for 17beta-estradiol-mediated inhibition of DmNobo enzymatic activity, as 17beta-estradiol did not inhibit and physically interacted less with the D113A DmNobo variant. Asp-113 is highly conserved among Nobo proteins, but not among other GSTs, implying that this residue is important for endogenous Nobo function. Indeed, a homozygous nobo allele with the D113A substitution exhibited embryonic lethality and an undifferentiated cuticle structure, a phenocopy of complete loss-of-function nobo homozygotes. These results suggest that the nobo family of GST proteins has acquired a unique amino acid residue that appears to be essential for binding an endogenous sterol substrate to regulate ecdysteroid biosynthesis. To the best of our knowledge, ours is the first study describing the structural characteristics of insect steroidogenic Halloween proteins. Our findings provide insights relevant for applied entomology to develop insecticides that specifically inhibit ecdysteroid biosynthesis. An integrated approach to unravel a crucial structural property required for the function of the insect steroidogenic Halloween protein Noppera-bo.,Koiwai K, Inaba K, Morohashi K, Enya S, Arai R, Kojima H, Okabe T, Fujikawa Y, Inoue H, Yoshino R, Hirokawa T, Kato K, Fukuzawa K, Shimada-Niwa Y, Nakamura A, Yumoto F, Senda T, Niwa R J Biol Chem. 2020 Apr 2. pii: RA119.011463. doi: 10.1074/jbc.RA119.011463. PMID:32241910 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione S-transferase 3D structures

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