2io7: Difference between revisions
New page: left|200px<br /><applet load="2io7" size="450" color="white" frame="true" align="right" spinBox="true" caption="2io7, resolution 2.7Å" /> '''E. coli Bifunctional ... |
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[[Image:2io7.jpg|left|200px]]<br /><applet load="2io7" size=" | [[Image:2io7.jpg|left|200px]]<br /><applet load="2io7" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2io7, resolution 2.7Å" /> | caption="2io7, resolution 2.7Å" /> | ||
'''E. coli Bifunctional glutathionylspermidine synthetase/amidase Incomplex with Mg2+ and AMPPNP'''<br /> | '''E. coli Bifunctional glutathionylspermidine synthetase/amidase Incomplex with Mg2+ and AMPPNP'''<br /> | ||
==Overview== | ==Overview== | ||
Most organisms use glutathione to regulate intracellular thiol redox | 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 Structure== | ==About this Structure== | ||
2IO7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with MG and ANP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 2IO7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IO7 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Chiang, B | [[Category: Chiang, B Y.]] | ||
[[Category: Chong, C | [[Category: Chong, C M.]] | ||
[[Category: Coward, J | [[Category: Coward, J K.]] | ||
[[Category: Ko, T | [[Category: Ko, T P.]] | ||
[[Category: Lin, C | [[Category: Lin, C H.]] | ||
[[Category: Pai, C | [[Category: Pai, C H.]] | ||
[[Category: Wang, A | [[Category: Wang, A H.J.]] | ||
[[Category: Yen, F | [[Category: Yen, F J.]] | ||
[[Category: ANP]] | [[Category: ANP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
[[Category: bifunctional glutathionylspermidine synthetase/amidase]] | [[Category: bifunctional glutathionylspermidine synthetase/amidase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:54:37 2008'' | ||
Revision as of 18:54, 21 February 2008
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E. coli Bifunctional glutathionylspermidine synthetase/amidase Incomplex with Mg2+ and AMPPNP
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
2IO7 is a Single protein structure of sequence from Escherichia coli with and as ligands. 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
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