1fpy

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spinqualitylabelsall models 1fpy, resolution 2.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF GLUTAMINE SYNTHETASE FROM SALMONELLA TYPHIMURIUM WITH INHIBITOR PHOSPHINOTHRICIN

Overview

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.

About this Structure

1FPY is a Single protein structure of sequence from Salmonella typhimurium with MN, ADP and PPQ as ligands. The following page contains interesting information on the relation of 1FPY with [Glutamine Synthetase]. Active as Glutamate--ammonia ligase, with EC number 6.3.1.2 Full crystallographic information is available from OCA.

Reference

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:11329256

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