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| {{STRUCTURE_2io7| PDB=2io7 | SCENE= }} | | {{STRUCTURE_2io7| PDB=2io7 | SCENE= }} |
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| '''E. coli Bifunctional glutathionylspermidine synthetase/amidase Incomplex with Mg2+ and AMPPNP'''
| | ===E. coli Bifunctional glutathionylspermidine synthetase/amidase Incomplex with Mg2+ and AMPPNP=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_17124497}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 17124497 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_17124497}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Yen, F J.]] | | [[Category: Yen, F J.]] |
| [[Category: Bifunctional glutathionylspermidine synthetase/amidase]] | | [[Category: Bifunctional glutathionylspermidine synthetase/amidase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:42:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 10:08:47 2008'' |