User:Kary Atkinson

From Proteopedia

Introduction

Glutamine synthetase is composed of twelve subunits, formed as two hexameric rings. The two rings are held together by twelve central loops which extend into the central region of the complex and include a small, four stranded β loop . 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 cleave specific residues. 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, via numerous hydrophobic interactions (hydrophobic regions are shown in purple) and four different hydrogen bonding interactions <insert wiki here showing hydrogen bonds>, of the quartenary structure of Glutamine synthetase.

References:

1. Fisher, M. T., Stadtman, E. R., Oxidative Modification of Escherichia coli Glutamine Synthetase, The Journal of Biological Chemistry, 1992, Vol 267. No3, 1872-1880

2. Moss, J., Stanley, S., Levine, R. L., Inactivation of Bacterial Glutamine Synthetase by ADP-ribosylation, The Journal of Biological Chemistry, 1990, Vol. 265, No. 34, 21056-21060

3. Yamashita, M. M., Almassy, R. J., Janson, C. A., Cascio, D., Eisenberg, D., Refined Atomic Model of Glutamine Synthetase at 3.5 A Resolution, The Journal of Biochemistry, 1989, Vol. 264, No. 30, 17681-17690