User:Kary Atkinson

From Proteopedia

Example of backbone trace with ligand exercise 1 Ligand and Chain Selection With Labeling exercise 2 Active Site Residues exercise 3 Going Solo exercise 4

Introduction

Glutamine synthetase is composed of twelve subunits, formed as two hexameric rings. The two rings are held together by ten central loops <insert wiki here showing the ten central loops> which extend into the central region of the complex and include a small, four stranded β loop <insert wiki here showing β loops>. Each loop is 33 residues long and has a convex shape <insert wiki here showing a central loop between subunits>. The spatial orientation <insert wiki here showing the central cavity, loop orientation and distance between> of the loops has been found to be less accessible for interactions to occur, contributing to the catalytic activity of the enzyme.

As all other enzymes, Glutamine synthetase contains an active site. However, unlike other enzymes it also contains a “passive site” known as the central loop (residues 156-188) where covalent modifications, with inhibitory effects are found. This segment of the complex is subject to proteolysis by four secreted proteases, which include the V8 protease from Staphylococcus aureus which cleaves after Glu-165, Subtilisin whose site of activity is unknown, chymotrypsin which cleaves after Tyr-164 and after Tyr-179, and trypsin which cleaves after Lys-169 and Lys-176. <insert wiki here showing the cleavage sites> This characteristic is unique and exclusive to the central loop as no other glutamine synthetase sites away from the central loop are attacked, under the same mild conditions, by these enzymes. Another covalent modification known to occur at central loop of Glutamine synthetase is ADP-ribosylation of Arg-172 <insert wiki here showing the ADP-ribosylation site>.

It is evident then that the central loop of glutamine synthetase (residues 156-188) is an important component of the enzyme, anchoring the subunits together and providing the spatial orientation necessary for activity. Therefore the central loop contributes both to the function and stabilization of Glutamine synthetase.