Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedN-acetylglutamate synthase (NAGS)1 catalyzes the first committed step in L-arginine biosynthesis in plants and micro-organisms and is subject to feedback inhibition by L-arginine. This study compares the crystal structures of NAGS from Neisseria gonorrhoeae (ngNAGS) in the inactive T-state with L-arginine bound and in the active R-state complexed with Co-enzyme A (CoA) and L-glutamate. Under all conditions examined, the enzyme consists of two stacked trimers. Each monomer has two domains-an amino acid kinase (AAK) domain with an AAK-like fold, but lacking kinase activity, and an N-acetyltransferase (NAT) domain homologous to other GCN5-related transferases. Binding of L-arginine to the AAK domain induces a global conformational change that increases the diameter of the hexamer by ~10 A and decreases its height by ~20 A. AAK dimers move 5 A outward along their two-fold axes and their tilt relative to the plane of the hexamer decreases by ~4 masculine. The NAT domains rotate ~109 masculine relative to AAK domains enabling new interdomain interactions. Interactions between AAK and NAT domains on different subunits also change. Local motions of several loops at the L-arginine binding site enable the protein to close around the bound ligand, while several loops at the NAT active site become disordered, markedly reducing enzymatic specific activity. Mechanism of allosteric inhibition of N-acetyl-L-glutamate synthase by L-arginine.,Min L, Jin Z, Caldovic L, Morizono H, Allewell NM, Tuchman M, Shi D J Biol Chem. 2008 Dec 18. PMID:19095660[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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