5g1n

Aspartate transcarbamoylase domain of human CAD bound to PALA

spinqualitylabelsall models 5g1n, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5g1n is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, PAL Related: 5g1o, 5g1p Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PYR1_HUMAN] This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). Publication Abstract from PubMed CAD, the multienzymatic protein that initiates and controls de novo synthesis of pyrimidines in animals, associates through its aspartate transcarbamoylase (ATCase) domain into particles of 1.5 MDa. Despite numerous structures of prokaryotic ATCases, we lack structural information on the ATCase domain of CAD. Here, we report the structure and functional characterization of human ATCase, confirming the overall similarity with bacterial homologs. Unexpectedly, human ATCase exhibits cooperativity effects that reduce the affinity for the anti-tumoral drug PALA. Combining structural, mutagenic, and biochemical analysis, we identified key elements for the necessary regulation and transmission of conformational changes leading to cooperativity between subunits. Mutation of one of these elements, R2024, was recently found to cause the first non-lethal CAD deficit. We reproduced this mutation in human ATCase and measured its effect, demonstrating that this arginine is part of a molecular switch that regulates the equilibrium between low- and high-affinity states for the ligands. Structure and Functional Characterization of Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral Drug PALA.,Ruiz-Ramos A, Velazquez-Campoy A, Grande-Garcia A, Moreno-Morcillo M, Ramon-Maiques S Structure. 2016 May 31. pii: S0969-2126(16)30079-X. doi:, 10.1016/j.str.2016.05.001. PMID:27265852 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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