title: Crystal structure of Type III glutamine synthetase: surprising reversal of the inter-ring interface.
abstract: Glutamine synthetases are ubiquitous, homo-oligomeric enzymes essential for nitrogen metabolism. Unlike types I and II, which are well described both structurally and functionally, the larger, type IIIs are poorly characterized despite their widespread occurrence. An understanding of the structural basis for this divergence and the implications for design of type-specific inhibitors has, therefore, been impossible. The first crystal structure of a GSIII enzyme, presented here, reveals a conservation of the GS catalytic fold but subtle differences in protein-ligand interactions suggest possible avenues for the design GSIII inhibitors. Despite these similarities, the divergence of the GSIII enzymes can be explained by differences in quaternary structure. Unexpectedly, the two hexameric rings of the GSIII dodecamer associate on the opposite surface relative to types I and II. The diversity of GS quaternary structures revealed here suggests a nonallosteric role for the evolution of the double-ringed architecture seen in all GS enzymes.
authors.affiliation: Electron Microscope Unit, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Jason M
authors.initials: JM
authors.lastname: van Rooyen
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Abratt
authors.forename: Hassan
authors.initials: H
authors.lastname: Belrhali
authors.forename: Trevor
authors.initials: T
authors.lastname: Sewell
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001441:Bacteroides fragilis / Q000201:enzymology* / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D005974:Glutamate-Ammonia Ligase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D007527:Isoenzymes; D008024:Ligands; D005974:Glutamate-Ammonia Ligase