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Yorodumi- PDB-8dbk: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer with resolved c... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8dbk | |||||||||
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Title | Human PRPS1 with Phosphate, ATP, and R5P; Hexamer with resolved catalytic loops | |||||||||
Components | Ribose-phosphate pyrophosphokinase 1 | |||||||||
Keywords | TRANSFERASE / phosphoribosyl pyrophosphate synthetase / ATP and R5P substrates / catalytic loop | |||||||||
Function / homology | Function and homology information 5-Phosphoribose 1-diphosphate biosynthesis / hypoxanthine biosynthetic process / ribose phosphate diphosphokinase complex / ribonucleoside monophosphate biosynthetic process / ribose-phosphate diphosphokinase / ribose phosphate diphosphokinase activity / 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 / ribonucleoside monophosphate biosynthetic process / ribose-phosphate diphosphokinase / ribose phosphate diphosphokinase activity / 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 | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.1 Å | |||||||||
Authors | Hvorecny, K.L. / Kollman, J.M. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2023 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: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8dbk.cif.gz | 320.6 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8dbk.ent.gz | 265.9 KB | Display | PDB format |
PDBx/mmJSON format | 8dbk.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8dbk_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 8dbk_full_validation.pdf.gz | 1.7 MB | Display | |
Data in XML | 8dbk_validation.xml.gz | 60.7 KB | Display | |
Data in CIF | 8dbk_validation.cif.gz | 84.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/db/8dbk ftp://data.pdbj.org/pub/pdb/validation_reports/db/8dbk | HTTPS FTP |
-Related structure data
Related structure data | 27287MC 8dbcC 8dbdC 8dbeC 8dbfC 8dbgC 8dbhC 8dbiC 8dbjC 8dblC 8dbmC 8dbnC 8dboC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 6 molecules ABCDEF
#1: Protein | Mass: 34835.121 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PRPS1 / Production host: Escherichia coli (E. coli) References: UniProt: P60891, ribose-phosphate diphosphokinase |
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-Sugars , 2 types, 6 molecules
#3: Sugar | ChemComp-HSX / #6: Sugar | ChemComp-PRP / | |
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-Non-polymers , 5 types, 36 molecules
#2: Chemical | ChemComp-ATP / #4: Chemical | ChemComp-PO4 / #5: Chemical | ChemComp-MG / #7: Chemical | ChemComp-AMP / | #8: Water | ChemComp-HOH / | |
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-Details
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 |
-Sample preparation
Component | Name: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phosphate, ATP, and R5P; resolved catalytic loops Type: COMPLEX Details: Six copies of PRPS1 assemble to form a hexamer; hexamers assembly linearly to form filaments. Here, two of the catalytic loops are well resolved. Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
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 |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 750 nm |
Image recording | Electron dose: 90 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.1 Å / Resolution method: FSC 0.5 CUT-OFF / Num. of particles: 788013 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT |