Structural highlights
2ioa is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| Related: | 2io7, 2io8, 2io9, 2iob |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GSP_ECOLI] Catalyzes the formation of an amide bond between glutathione and spermidine coupled with hydrolysis of ATP; also catalyzes the hydrolysis of glutathionylspermidine to glutathione and spermidine.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Most organisms use glutathione to regulate intracellular thiol redox balance and protect against oxidative stress; protozoa, however, utilize trypanothione for this purpose. Trypanothione biosynthesis requires ATP-dependent conjugation of glutathione (GSH) to the two terminal amino groups of spermidine by glutathionylspermidine synthetase (GspS) and trypanothione synthetase (TryS), which are considered as drug targets. GspS catalyzes the penultimate step of the biosynthesis-amide bond formation between spermidine and the glycine carboxylate of GSH. We report herein five crystal structures of Escherichia coli GspS in complex with substrate, product or inhibitor. The C-terminal of GspS belongs to the ATP-grasp superfamily with a similar fold to the human glutathione synthetase. GSH is likely phosphorylated at one of two GSH-binding sites to form an acylphosphate intermediate that then translocates to the other site for subsequent nucleophilic addition of spermidine. We also identify essential amino acids involved in the catalysis. Our results constitute the first structural information on the biochemical features of parasite homologs (including TryS) that underlie their broad specificity for polyamines.
Dual binding sites for translocation catalysis by Escherichia coli glutathionylspermidine synthetase.,Pai CH, Chiang BY, Ko TP, Chou CC, Chong CM, Yen FJ, Chen S, Coward JK, Wang AH, Lin CH EMBO J. 2006 Dec 13;25(24):5970-82. Epub 2006 Nov 23. PMID:17124497[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pai CH, Chiang BY, Ko TP, Chou CC, Chong CM, Yen FJ, Chen S, Coward JK, Wang AH, Lin CH. Dual binding sites for translocation catalysis by Escherichia coli glutathionylspermidine synthetase. EMBO J. 2006 Dec 13;25(24):5970-82. Epub 2006 Nov 23. PMID:17124497
