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Biol 430 Biology Major Partners: Delo Sarr, Mustafa Husain

Glutamine synthase

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Contents

Jmol practice

Backbone with ligand

Labeled Ligands in Chain A

Active Site with Amino Acid Residues

Connection between Chain F residue 63 and Chain G residue 319

Stoichiometry

The stoichiometry of Glutamine Synthetase is as follows: Glutamate + NHз + ATP --> Glutamine + ADP + Pi + H+

In this reaction, Glutamate is used as a major reactant and ATP is used for energy to form Glutamine. It should be noted that along with the enzyme, Me+ which can be either manganese or magnesium is used as a catalyst.

This is however, a 2-step reaction. In the first step of this reaction, an intermediate Υ-glutamyl phosphate is formed. The formation of the intermediate is done by phosphoryl transfer an ATP group Y-carboxylate group of glutamate. In the second step of this reaction, NHз attacks the activated intermediate to release the phosphate group yielding Glutamine.

Quarternary Structure Polymerization

The enzyme Glutamine Synthetase is made up of 12 polypeptide monomers. The structure is separated into 2 identical hexameric rings held together by hydrophobic and hydrogen bonding forces. Each monomer consists of a C and N terminus, exposed to hydrophilic and hydrophobic regions. The N-terminal helix is exposed to hydrophilic solvent, where as the C-terminal is concealed in a hydrophobic regions inside the helical structure of the rings. The central channel is linked together by six four-stranded anti-parallel L-sheets which along with the 12 monomers enhance the stability of the ring structure.

Active Site

In this enzyme, there are 12 similar subunits bonded to each other. Each subunit has an active site. The active site of glutamine synthetase lies primarily around 3 manganese atoms. It is surrounded by 3 important ligands: MPD, ADP, TL as labeled in the applet. ADP is short for Adenosite Diphosphate. The ligand MPD is (4s)-2-methyl-2,4-pentanediol. And the metal ion, Thallium is also labeled in the applet.

Glutamine Synthetase Symmetry


Reference

1. Eisenberg, David and Gill, Harindarpal and Pfluegl, Gaston and Rotstein, Sergio. “Structure-function relationships of glutamine synthetases.” Elsevier, archives of biochemistry and biophysics 1477(Dec 1999):122-123.

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Kay Owosela, Eran Hodis

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