4k30 | pdb_00004k30

Structure of the N-acetyltransferase domain of human N-acetylglutamate synthase

spinqualitylabelsall models 4k30, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4k30 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NLG Gene: NAGS (HUMAN) Activity: Amino-acid N-acetyltransferase, with EC number 2.3.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NAGS_HUMAN] Hyperammonemia due to N-acetylglutamate synthetase deficiency. The disease is caused by mutations affecting the gene represented in this entry. Function [NAGS_HUMAN] Plays a role in the regulation of ureagenesis by producing variable amounts of N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPSI) activity. Publication Abstract from PubMed N-acetylglutamate synthase (NAGS) catalyzes the conversion of AcCoA and L-glutamate to CoA and N-acetyl-L-glutamate (NAG), an obligate cofactor for carbamyl phosphate synthetase I (CPSI) in the urea cycle. NAGS deficiency results in elevated levels of plasma ammonia which is neurotoxic. We report herein the first crystal structure of human NAGS, that of the catalytic N-acetyltransferase (hNAT) domain with N-acetyl-L-glutamate bound at 2.1 A resolution. Functional studies indicate that the hNAT domain retains catalytic activity in the absence of the amino acid kinase (AAK) domain. Instead, the major functions of the AAK domain appear to be providing a binding site for the allosteric activator, L-arginine, and an N-terminal proline-rich motif that is likely to function in signal transduction to CPS1. Crystalline hNAT forms a dimer similar to the NAT-NAT dimers that form in crystals of bifunctional N-acetylglutamate synthase/kinase (NAGS/K) from Maricaulis maris and also exists as a dimer in solution. The structure of the NAG binding site, in combination with mutagenesis studies, provide insights into the catalytic mechanism. We also show that native NAGS from human and mouse exists in tetrameric form, similar to those of bifunctional NAGS/K. Crystal structure of the N-acetyltransferase domain of human N-acetyl-L-glutamate synthase in complex with N-acetyl-L-glutamate provides insights into its catalytic and regulatory mechanisms.,Zhao G, Jin Z, Allewell NM, Tuchman M, Shi D PLoS One. 2013 Jul 24;8(7):e70369. doi: 10.1371/journal.pone.0070369. Print 2013. PMID:23894642 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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