Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Evolutionarily divergent Mycobacterium tuberculosis CTP synthase filaments are under selective pressure.
Journal, issue, pages	Nat Commun, Vol. 16, Issue 1, Page 5993, Year 2025
Publish date	Jul 1, 2025
Authors	Eric M Lynch / Yao Lu / Jin Ho Park / Lin Shao / Justin M Kollman / E Hesper Rego /
PubMed Abstract	The final and rate-limiting enzyme in pyrimidine biosynthesis, cytidine triphosphate synthase (CTPS), is essential for the viability of Mycobacterium tuberculosis and other mycobacteria. Its product, ...The final and rate-limiting enzyme in pyrimidine biosynthesis, cytidine triphosphate synthase (CTPS), is essential for the viability of Mycobacterium tuberculosis and other mycobacteria. Its product, cytidine triphosphate (CTP), is critical for RNA, DNA, lipid and cell wall synthesis, and is involved in chromosome segregation. In various organisms across the tree of life, CTPS assembles into higher-order filaments, leading us to hypothesize that M. tuberculosis CTPS (mtCTPS) also forms higher-order structures. Here, we show that mtCTPS does assemble into filaments but with an unusual architecture not seen in other organisms. Through a combination of structural, biochemical, and cellular techniques, we show that polymerization stabilizes the active conformation of the enzyme and resists product inhibition, potentially allowing for the highly localized production of CTP within the cell. Indeed, CTPS filaments localize near the CTP-dependent complex needed for chromosome segregation, and cells expressing mutant enzymes unable to polymerize are altered in their ability to robustly form this complex. Intriguingly, mutants that inhibit filament formation are under positive selection in clinical isolates of M. tuberculosis, pointing to a critical role needed to withstand pressures imposed by the host and/or antibiotics. Taken together, our data reveal an unexpected mechanism for the spatially organized production of a critical nucleotide in M. tuberculosis, which may represent a vulnerability of the pathogen that can be exploited with chemotherapy.
External links	Nat Commun / PubMed:40593557 / PubMed Central
Methods	EM (single particle)
Resolution	2.8 - 3.6 Å
Structure data	42605 8uv4 EMDB-42605, PDB-8uv4: M. tuberculosis CTP synthase filament bound to substrates Method: EM (single particle) / Resolution: 3.2 Å 42611 8uv8 EMDB-42611, PDB-8uv8: M. tuberculosis CTP synthase tetramer bound to CTP Method: EM (single particle) / Resolution: 3.6 Å 42612 8uv9 EMDB-42612, PDB-8uv9: M. tuberculosis CTP synthase bound to inhibitor GSK1570606A Method: EM (single particle) / Resolution: 2.8 Å 42613 8uva EMDB-42613, PDB-8uva: M. tuberculosis CTP synthase bound to inhibitor GSK735826A Method: EM (single particle) / Resolution: 2.8 Å
Chemicals	ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-5ZL: [[(2~{R},3~{S},4~{R},5~{R})-3,4-bis(oxidanyl)-5-(2-oxidanyl-4-phosphonooxy-pyrimidin-1-yl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl] phosphono hydrogen phosphate ChemComp-MG: Unknown entry ChemComp-CTP: CYTIDINE-5'-TRIPHOSPHATE ChemComp-GLN: GLUTAMINE ChemComp-Q2N: 2-(4-fluorophenyl)-~{N}-(4-pyridin-2-yl-1,3-thiazol-2-yl)ethanamide ChemComp-UTP: URIDINE 5'-TRIPHOSPHATE / UTPYM ChemComp, No image ChemComp-XMW: Unknown entry
Source	mycobacterium tuberculosis (bacteria)
Keywords	LIGASE / metabolic enzyme / filament