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Open data
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Basic information
Entry | Database: PDB / ID: 8dbc | |||||||||
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Title | Human PRPS1 with Phosphate; Hexamer | |||||||||
![]() | Ribose-phosphate pyrophosphokinase 1 | |||||||||
![]() | TRANSFERASE / phosphoribosyl pyrophosphate synthetase / phosphate | |||||||||
Function / homology | ![]() 5-Phosphoribose 1-diphosphate biosynthesis / hypoxanthine biosynthetic process / ribose phosphate diphosphokinase complex / ribose-phosphate diphosphokinase / ribose phosphate diphosphokinase activity / ribonucleoside monophosphate biosynthetic process / urate biosynthetic process / 5-phosphoribose 1-diphosphate biosynthetic process / pyrimidine nucleotide biosynthetic process / purine nucleotide biosynthetic process ...5-Phosphoribose 1-diphosphate biosynthesis / hypoxanthine biosynthetic process / ribose phosphate diphosphokinase complex / ribose-phosphate diphosphokinase / ribose phosphate diphosphokinase activity / ribonucleoside monophosphate biosynthetic process / urate biosynthetic process / 5-phosphoribose 1-diphosphate biosynthetic process / pyrimidine nucleotide biosynthetic process / purine nucleotide biosynthetic process / purine nucleobase metabolic process / kinase activity / nervous system development / magnesium ion binding / protein homodimerization activity / ATP binding / identical protein binding / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Hvorecny, K.L. / Kollman, J.M. | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Human PRPS1 filaments stabilize allosteric sites to regulate activity. Authors: Kelli L Hvorecny / Kenzee Hargett / Joel D Quispe / Justin M Kollman / ![]() 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. | |||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 305.7 KB | Display | ![]() |
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PDB format | ![]() | 255.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 27279MC ![]() 8dbdC ![]() 8dbeC ![]() 8dbfC ![]() 8dbgC ![]() 8dbhC ![]() 8dbiC ![]() 8dbjC ![]() 8dbkC ![]() 8dblC ![]() 8dbmC ![]() 8dbnC ![]() 8dboC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 34879.238 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P60891, ribose-phosphate diphosphokinase #2: Chemical | ChemComp-PO4 / Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phosphate Type: COMPLEX Details: Six copies of PRPS1 assemble to form a hexamer; hexamers assembly linearly to form filaments. Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.6 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid type: C-flat |
Vitrification | Instrument: HOMEMADE PLUNGER / Cryogen name: ETHANE |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 750 nm |
Image recording | Electron dose: 60 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: D3 (2x3 fold dihedral) | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.2 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 158965 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT |