2IOA: E. Coli Bifunctional Glutathionylspermidine SynthetaseAMIDASE INCOMPLEX WITH MG2+ AND ADP AND Phosphinate Inhibitor

Citation:
Abstract
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.
PDB ID: 2IOADownload
MMDB ID: 43430
PDB Deposition Date: 2006/10/10
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 2IOA: dimeric; determined by author and by software (PISA)
Molecular Components in 2IOA
Label Count Molecule
Proteins (2 molecules)
2
Bifunctional Glutathionylspermidine Synthetase/amidase(Gene symbol: gss)
Molecule annotation
Chemicals (8 molecules)
1
4
2
2
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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