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	Human PRPS1 filaments stabilize allosteric sites to regulate activity.
Journal, issue, pages	Nat Struct Mol Biol, Vol. 30, Issue 3, Page 391-402, Year 2023
Publish date	Feb 6, 2023
Authors	Kelli L Hvorecny / Kenzee Hargett / Joel D Quispe / Justin M Kollman /
PubMed Abstract	The universally conserved enzyme phosphoribosyl pyrophosphate synthetase (PRPS) assembles filaments in evolutionarily diverse organisms. PRPS is a key regulator of nucleotide metabolism, and ...The universally conserved enzyme phosphoribosyl pyrophosphate synthetase (PRPS) assembles filaments in evolutionarily diverse organisms. PRPS is a key regulator of nucleotide metabolism, and mutations in the human enzyme PRPS1 lead to a spectrum of diseases. Here we determine structures of human PRPS1 filaments in active and inhibited states, with fixed assembly contacts accommodating both conformations. The conserved assembly interface stabilizes the binding site for the essential activator phosphate, increasing activity in the filament. Some disease mutations alter assembly, supporting the link between filament stability and activity. Structures of active PRPS1 filaments turning over substrate also reveal coupling of catalysis in one active site with product release in an adjacent site. PRPS1 filaments therefore provide an additional layer of allosteric control, conserved throughout evolution, with likely impact on metabolic homeostasis. Stabilization of allosteric binding sites by polymerization adds to the growing diversity of assembly-based enzyme regulatory mechanisms.
External links	Nat Struct Mol Biol / PubMed:36747094 / PubMed Central
Methods	EM (single particle)
Resolution	2.0 - 3.2 Å
Structure data	27279 8dbc EMDB-27279, PDB-8dbc: Human PRPS1 with Phosphate; Hexamer Method: EM (single particle) / Resolution: 3.2 Å 27280 8dbd EMDB-27280, PDB-8dbd: Human PRPS1 with Phosphate; Filament Interface Method: EM (single particle) / Resolution: 3.2 Å 27281 8dbe EMDB-27281, PDB-8dbe: Human PRPS1 with ADP; Hexamer Method: EM (single particle) / Resolution: 2.1 Å 27282 8dbf EMDB-27282, PDB-8dbf: Human PRPS1 with ADP; Filament Interface Method: EM (single particle) / Resolution: 2.2 Å 27283 8dbg EMDB-27283, PDB-8dbg: Human PRPS1 with Phosphate and ATP; Hexamer Method: EM (single particle) / Resolution: 2.2 Å 27284 8dbh EMDB-27284, PDB-8dbh: Human PRPS1 with Phosphate and ATP; Filament Interface Method: EM (single particle) / Resolution: 2.2 Å 27285 8dbi EMDB-27285, PDB-8dbi: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer Method: EM (single particle) / Resolution: 2.0 Å 27286 8dbj EMDB-27286, PDB-8dbj: Human PRPS1 with Phosphate, ATP, and R5P; Filament Interface Method: EM (single particle) / Resolution: 2.0 Å 27287 8dbk EMDB-27287, PDB-8dbk: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer with resolved catalytic loops Method: EM (single particle) / Resolution: 2.1 Å EMDB-27288: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer with resolved catalytic loops Method: EM (single particle) / Resolution: 2.1 Å 27289 8dbl EMDB-27289, PDB-8dbl: Human PRPS1 with Phosphate and PRPP; Hexamer Method: EM (single particle) / Resolution: 2.4 Å 27290 8dbm EMDB-27290, PDB-8dbm: Human PRPS1 with Phosphate and PRPP; Filament Interface Method: EM (single particle) / Resolution: 2.4 Å 27291 8dbn EMDB-27291, PDB-8dbn: Human PRPS1-E307A engineered mutation with Phosphate, ATP, and R5P; Hexamer Method: EM (single particle) / Resolution: 2.4 Å EMDB-27292: Human PRPS1-E307A engineered mutation with Phosphate, ATP, and R5P; Symmetry-expanded Hexamer Method: EM (single particle) / Resolution: 2.6 Å 27293 8dbo EMDB-27293, PDB-8dbo: Human PRPS1-E307A engineered mutation with ADP; Hexamer Method: EM (single particle) / Resolution: 2.5 Å EMDB-27294: Human PRPS1-E307A engineered mutation with ADP; Symmetry-expanded Hexamer 1 Method: EM (single particle) / Resolution: 2.5 Å EMDB-27295: Human PRPS1-E307A engineered mutation with ADP; Symmetry-expanded Hexamer 2 Method: EM (single particle) / Resolution: 2.6 Å
Chemicals	ChemComp-PO4: PHOSPHATE ION ChemComp-HSX: 5-O-phosphono-alpha-D-ribofuranose ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying moleculeYM ChemComp-MG: Unknown entry ChemComp-HOH: WATER ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying moleculeYM ChemComp-PRP: 1-O-pyrophosphono-5-O-phosphono-alpha-D-ribofuranose ChemComp-AMP: ADENOSINE MONOPHOSPHATE / AMP*YM
Source	homo sapiens (human)
Keywords	TRANSFERASE / phosphoribosyl pyrophosphate synthetase / phosphate / phosphate activator / ADP inhibitor / ATP substrate / ATP and R5P substrates / catalytic loop / PRPP product / ATP/R5P substrate / Filament-breaking mutation