Glutamine synthetase structure‐catalysis relationship—Recent advances and applications

Abstract

Glutamine synthetase is a key enzyme that exists in every living organism. It is responsible for incorporating ammonium into glutamate, generating glutamine. Research on this enzyme has grown substantially over the last decades. The recent advances in the determination of its structure, through the crystallization of novel classes of glutamine synthetase with increased resolution, greatly contributed to a shift in the glutamine synthetase research from fundamental to more applied. Here, we explore the active sites of glutamine synthetases, review the structural and catalytic roles of their active sites' ions Mg 2+ s, combine the information gathered from recent computational studies dedicated to unravel their catalytic mechanisms with the hypothesis raised at the beginning of the XXI century based on experimental studies, glance at the development of competitive glutamine synthetase inhibitors, and highlight the high value of these enzymes to industry, namely in the fields of agriculture and medicine.

Involvement of glutamine synthetase 2 (GS2) amplification and overexpression in Amaranthus palmeri resistance to glufosinate

“…Glutamine synthetase, the target of GFA, is a vital enzyme present in all living organisms. Enzymes in this family are classified as Type I, II or III based on its primary and quaternary structures (dos Santos Moreira et al 2019 ). In plants, GS can be further categorized according to their subcellular location: GS1 enzymes are cytosolic, and GS2 enzymes are plastidic (Bernard and Habash 2009 ).…”

2-oxoglutarate triggers assembly of active dodecamericMethanosarcina mazeiglutamine synthetase

“…The enzyme, its structure and regulation has been investigated in detail in different organisms for more than half a century (e.g. Dos Santos Moreira et al, 2019; Stadtman, 2001; Woolfolk and Stadtman, 1967).…”

“…Most of the GS are grouped into three major classes based on their monomeric size and oligomerization properties (overview in Dos Santos Moreira et al, 2019). GSI and GSIII, both found in bacteria and archaea mostly form dodecamers, whereas GSII found in Eukaryotes form decamers of smaller subunits (Dos Santos Moreira et al, 2019; He et al, 2009; Valentine et al, 1968; van Rooyen et al, 2011). The GSI class can be further grouped into Iα-type GS and Iβ-type GS based on their amino acid sequence and respective molecular mechanisms of activity regulation.…”