8i9o

ecCTPS filament bound with CTP, NADH, DON

spinqualitylabelsall models 8i9o, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8i9o is a 4 chain structure with sequence from Escherichia coli 'BL21-Gold(DE3)pLysS AG'. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.9Å Ligands: ADE, CTP, MG, ONL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PYRG_ECOLI Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.[HAMAP-Rule:MF_01227] Publication Abstract from PubMed Cytidine triphosphate synthase (CTPS) plays a pivotal role in the de novo synthesis of cytidine triphosphate (CTP), a fundamental building block for RNA and DNA that is essential for life. CTPS is capable of directly binding to all four nucleotide triphosphates: adenine triphosphate, uridine triphosphate, CTP, and guanidine triphosphate. Furthermore, CTPS can form cytoophidia in vivo and metabolic filaments in vitro, undergoing regulation at multiple levels. CTPS is considered a potential therapeutic target for combating invasions or infections by viral or prokaryotic pathogens. Utilizing cryo-electron microscopy, we determined the structure of Escherichia coli CTPS (ecCTPS) filament in complex with CTP, nicotinamide adenine dinucleotide (NADH), and the covalent inhibitor 6-diazo-5-oxo- l-norleucine (DON), achieving a resolution of 2.9 A. We constructed a phylogenetic tree based on differences in filament-forming interfaces and designed a variant to validate our hypothesis, providing an evolutionary perspective on CTPS filament formation. Our computational analysis revealed a solvent-accessible ammonia tunnel upon DON binding. Through comparative structural analysis, we discern a distinct mode of CTP binding of ecCTPS that differs from eukaryotic counterparts. Combining biochemical assays and structural analysis, we determined and validated the synergistic inhibitory effects of CTP with NADH or adenine on CTPS. Our results expand our comprehension of the diverse regulatory aspects of CTPS and lay a foundation for the design of specific inhibitors targeting prokaryotic CTPS. Filamentation and inhibition of prokaryotic CTP synthase with ligands.,Guo C, Wang Z, Liu JL mLife. 2024 May 2;3(2):240-250. doi: 10.1002/mlf2.12119. eCollection 2024 Jun. PMID:38948148 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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