2iob
|
E. coli Bifunctional glutathionylspermidine synthetase/amidase Apo protein
OverviewOverview
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.
About this StructureAbout this Structure
2IOB is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
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
Page seeded by OCA on Wed Nov 21 12:23:56 2007