Advances in the enzymology of glutamine synthesis.

Meister's proposal of a gamma-glutamyl-P intermediate in the glutamine synthetase reaction set the scene for understanding how the stepwise activation of the carboxyl group greatly increased its susceptibility toward nucleophilic attack and amide bond synthesis. Topics covered in this review include: the discovery of the enzymatic synthesis of glutamine; the role of glutamine synthetase in defining the thermodynamics of ATPases; early isotopic tracer studies of the synthetase reaction; the proposed intermediacy of gamma-glutamyl-phosphate; the mechanism of methionine sulfoximine inhibition; stereochemical mapping of the enzyme's active site; detection of enzyme reaction cycle intermediates; borohydride trapping of gamma-glutamyl-P; positional isotope exchanges catalyzed by glutamine synthetase; regulation of bacterial enzyme; and a brief account of how knowledge of the atomic structure of bacterial glutamine synthetase has clarified ligand binding interactions. Concluding remarks also address how the so-called "Protein Ligase Problem" may be solved by extending the catalytic versatility of carboxyl-group activating enzymes.