1F1H

CRYSTAL STRUCTURE OF GLUTAMINE SYNTHETASE FROM SALMONELLA TYPHIMURIUM WITH THALLIUM IONS

Summary for 1F1H

• Entry DOI: 10.2210/pdb1f1h/pdb
• Descriptor: PROTEIN (GLUTAMINE SYNTHETASE), MANGANESE (II) ION, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: glutamine synthetase, thallium ions, ligase
• Biological source: Salmonella typhimurium
• Total number of polymer chains: 12
• Total formula weight: 633701.22

Authors

Gill, H.S.,Eisenberg, D. (deposition date: 2000-05-19, release date: 2001-04-04, Last modification date: 2024-02-07)

Primary citation

Gill, H.S.,Eisenberg, D.
The crystal structure of phosphinothricin in the active site of glutamine synthetase illuminates the mechanism of enzymatic inhibition.
Biochemistry, 40:1903-1912, 2001

PubMed Abstract: 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.

PubMed: 11329256
DOI: 10.1021/bi002438h

Experimental method

X-RAY DIFFRACTION (2.67 Å)