1fpy

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[[Image:1fpy.gif|left|200px]]
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==Overview==
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{{ABSTRACT_11329256}}
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Phosphinothricin is a potent inhibitor of the enzyme glutamine synthetase (GS). The resolution of the native structure of GS from Salmonella typhimurium has been extended to 2.5 A resolution, and the improved model is used to determine the structure of phosphinothricin complexed to GS by difference Fourier methods. The structure suggests a noncovalent, dead-end mechanism of inhibition. Phosphinothricin occupies the glutamate substrate pocket and stabilizes the Glu327 flap in a position which blocks the glutamate entrance to the active site, trapping the inhibitor on the enzyme. One oxygen of the phosphinyl group of phosphinothricin appears to be protonated, because of its proximity to the carboxylate group of Glu327. The other phosphinyl oxygen protrudes into the negatively charged binding pocket for the substrate ammonium, disrupting that pocket. The distribution of charges in the glutamate binding pocket is complementary to those of phosphinothricin. The presence of a second ammonium binding site within the active site is confirmed by its analogue thallous ion, marking the ammonium site and its protein ligands. The inhibition of GS by methionine sulfoximine can be explained by the same mechanism. These models of inhibited GS further illuminate its catalytic mechanism.
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==About this Structure==
==About this Structure==
1FPY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium]. The following page contains interesting information on the relation of 1FPY with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb30_1.html Glutamine Synthetase]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FPY OCA].
1FPY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Salmonella_typhimurium Salmonella typhimurium]. The following page contains interesting information on the relation of 1FPY with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb30_1.html Glutamine Synthetase]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FPY OCA].
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==Reference==
 
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The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition., Gill HS, Eisenberg D, Biochemistry. 2001 Feb 20;40(7):1903-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11329256 11329256]
 
[[Category: Glutamate--ammonia ligase]]
[[Category: Glutamate--ammonia ligase]]
[[Category: Glutamine Synthetase]]
[[Category: Glutamine Synthetase]]
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[[Category: Inhibition]]
[[Category: Inhibition]]
[[Category: Phosphinothricin]]
[[Category: Phosphinothricin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:37:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 26 17:22:56 2008''

Revision as of 14:22, 26 June 2008

Image:1fpy.png

Template:STRUCTURE 1fpy

CRYSTAL STRUCTURE OF GLUTAMINE SYNTHETASE FROM SALMONELLA TYPHIMURIUM WITH INHIBITOR PHOSPHINOTHRICIN


Template:ABSTRACT 11329256

About this Structure

1FPY is a Single protein structure of sequence from Salmonella typhimurium. The following page contains interesting information on the relation of 1FPY with [Glutamine Synthetase]. Full crystallographic information is available from OCA.

Page seeded by OCA on Thu Jun 26 17:22:56 2008

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