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	Structural basis for ligand binding modes of CTP synthase.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 118, Issue 30, Year 2021
Publish date	Jul 27, 2021
Authors	Xian Zhou / Chen-Jun Guo / Chia-Chun Chang / Jiale Zhong / Huan-Huan Hu / Guang-Ming Lu / Ji-Long Liu /
PubMed Abstract	Cytidine triphosphate synthase (CTPS), which comprises an ammonia ligase domain and a glutamine amidotransferase domain, catalyzes the final step of de novo CTP biosynthesis. The activity of CTPS is ...Cytidine triphosphate synthase (CTPS), which comprises an ammonia ligase domain and a glutamine amidotransferase domain, catalyzes the final step of de novo CTP biosynthesis. The activity of CTPS is regulated by the binding of four nucleotides and glutamine. While glutamine serves as an ammonia donor for the ATP-dependent conversion of UTP to CTP, the fourth nucleotide GTP acts as an allosteric activator. Models have been proposed to explain the mechanisms of action at the active site of the ammonia ligase domain and the conformational changes derived by GTP binding. However, actual GTP/ATP/UTP binding modes and relevant conformational changes have not been revealed fully. Here, we report the discovery of binding modes of four nucleotides and a glutamine analog 6-diazo-5-oxo-L-norleucine in CTPS by cryo-electron microscopy with near-atomic resolution. Interactions between GTP and surrounding residues indicate that GTP acts to coordinate reactions at both domains by directly blocking ammonia leakage and stabilizing the ammonia tunnel. Additionally, we observe the ATP-dependent UTP phosphorylation intermediate and determine interacting residues at the ammonia ligase. A noncanonical CTP binding at the ATP binding site suggests another layer of feedback inhibition. Our findings not only delineate the structure of CTPS in the presence of all substrates but also complete our understanding of the underlying mechanisms of the allosteric regulation and CTP synthesis.
External links	Proc Natl Acad Sci U S A / PubMed:34301892 / PubMed Central
Methods	EM (single particle)
Resolution	2.48 - 3.2 Å
Structure data	30810 7dpt EMDB-30810, PDB-7dpt: Structural basis for ligand binding modes of CTP synthase Method: EM (single particle) / Resolution: 2.48 Å 30811 7dpw EMDB-30811, PDB-7dpw: Structural basis for ligand binding modes of CTP synthase Method: EM (single particle) / Resolution: 2.65 Å 32541 7wiz EMDB-32541, PDB-7wiz: Structural basis for ligand binding modes of CTP synthase Method: EM (single particle) / Resolution: 3.2 Å 32542 7wj4 EMDB-32542, PDB-7wj4: Structural basis for ligand binding modes of CTP synthase Method: EM (single particle) / Resolution: 3.15 Å
Chemicals	ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying moleculeYM / Guanosine triphosphate ChemComp-DON: 6-DIAZENYL-5-OXO-L-NORLEUCINE ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM / Adenosine diphosphate ChemComp-MG: Unknown entry 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-HOH: WATER / Water ChemComp-CTP: CYTIDINE-5'-TRIPHOSPHATE / Cytidine triphosphate ChemComp-GLN: GLUTAMINE / Glutamine ChemComp-ACP: PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER / AMP-PCP, energy-carrying molecule analogueYM ChemComp-UTP: URIDINE 5'-TRIPHOSPHATE / UTPYM / Uridine triphosphate ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM / Adenosine triphosphate ChemComp-GGL*: GAMMA-L-GLUTAMIC ACID / Glutamic acid
Source	drosophila melanogaster (fruit fly)
Keywords	LIGASE / substrate-bound / filament / DON / product-bound / CTP / CTPS