ArticlePloS one2013
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.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature.Orphanet journal of rare diseases · 2020Pooled it
- Use of pure recombinant human enzymes to assess the disease-causing potential of missense mutations in urea cycle disorders, applied to N-acetylglutamate synthase deficiency.Journal of inherited metabolic disease · 2024Article
- Datamining approaches for examining the low prevalence of N-acetylglutamate synthase deficiency and understanding transcriptional regulation of urea cycle genes.Journal of inherited metabolic disease · 2024Article
- RNA-seq analysis of small intestine transcriptional changes induced by starvation stress in piglets.Animal biotechnology · 2024Article
- Article
- Insight into de-regulation of amino acid feedback inhibition: a focus on structure analysis method.Microbial cell factories · 2023Review
- Mitochondrial transport and metabolism of the vitamin B-derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NADIUBMB life · 2022Review
- Article
- Gene delivery corrects N-acetylglutamate synthase deficiency and enables insights in the physiological impact of L-arginine activation of N-acetylglutamate synthase.Scientific reports · 2021Article
- Mitochondrial Enzymes of the Urea Cycle Cluster at the Inner Mitochondrial Membrane.Frontiers in physiology · 2020Article
- Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult Case Presenting with Headaches and Review of the Literature.International journal of molecular sciences · 2018Review
- DNA Sliding Clamps as Therapeutic Targets.Frontiers in molecular biosciences · 2018Review
- Effect of arginine on oligomerization and stability of N-acetylglutamate synthase.Scientific reports · 2016Article
- The N-Acetylglutamate Synthase Family: Structures, Function and Mechanisms.International journal of molecular sciences · 2015Review
- Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L-glutamate synthase/kinase with and without a His tag bound to N-acetyl-L-glutamate.Acta crystallographica. Section F, Structural biology communications · 2015Article
- Structural, kinetic and proteomic characterization of acetyl phosphate-dependent bacterial protein acetylation.PloS one · 2014Article
- Structure of N-acetyl-L-glutamate synthase/kinase from Maricaulis maris with the allosteric inhibitor L-arginine bound.Biochemical and biophysical research communications · 2013Article
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5 authors.
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Abstract
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 Å 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.
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