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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Human PRPS1 with Phosphate and PRPP; Hexamer | |||||||||
![]() | Human PRPS1 with Phosphate and PRPP; Hexamer Centered | |||||||||
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![]() | phosphoribosyl pyrophosphate synthetase / PRPP product / TRANSFERASE | |||||||||
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 / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | |||||||||
![]() | Hvorecny KL / Kollman JM | |||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 6.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.8 KB 16.8 KB | Display Display | ![]() |
Images | ![]() | 116.1 KB | ||
Filedesc metadata | ![]() | 5.8 KB | ||
Others | ![]() ![]() | 49.6 MB 49.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 721 KB | Display | ![]() |
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Full document | ![]() | 720.5 KB | Display | |
Data in XML | ![]() | 12.5 KB | Display | |
Data in CIF | ![]() | 14.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dblMC ![]() 8dbcC ![]() 8dbdC ![]() 8dbeC ![]() 8dbfC ![]() 8dbgC ![]() 8dbhC ![]() 8dbiC ![]() 8dbjC ![]() 8dbkC ![]() 8dbmC ![]() 8dbnC ![]() 8dboC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Human PRPS1 with Phosphate and PRPP; Hexamer Centered | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.058 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Human PRPS1 with Phosphate and PRPP; Hexamer Centered half 1
File | emd_27289_half_map_1.map | ||||||||||||
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Annotation | Human PRPS1 with Phosphate and PRPP; Hexamer Centered half 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Human PRPS1 with Phosphate and PRPP; Hexamer Centered half 2
File | emd_27289_half_map_2.map | ||||||||||||
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Annotation | Human PRPS1 with Phosphate and PRPP; Hexamer Centered half 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phospha...
Entire | Name: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phosphate and PRPP |
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Components |
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-Supramolecule #1: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phospha...
Supramolecule | Name: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phosphate and PRPP type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 Details: Six copies of PRPS1 assemble to form a hexamer; hexamers assembly linearly to form filaments. |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Ribose-phosphate pyrophosphokinase 1
Macromolecule | Name: Ribose-phosphate pyrophosphokinase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO / EC number: ribose-phosphate diphosphokinase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 34.835121 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SPNIKIFSGS SHQDLSQKIA DRLGLELGKV VTKKFSNQET CVEIGESVRG EDVYIVQSGC GEINDNLMEL LIMINACKIA SASRVTAVI PCFPYARQDK KDKSRAPISA KLVANMLSVA GADHIITMDL HASQIQGFFD IPVDNLYAEP AVLKWIRENI S EWRNCTIV ...String: SPNIKIFSGS SHQDLSQKIA DRLGLELGKV VTKKFSNQET CVEIGESVRG EDVYIVQSGC GEINDNLMEL LIMINACKIA SASRVTAVI PCFPYARQDK KDKSRAPISA KLVANMLSVA GADHIITMDL HASQIQGFFD IPVDNLYAEP AVLKWIRENI S EWRNCTIV SPDAGGAKRV TSIADRLNVD FALIHKERKK ANEVDRMVLV GDVKDRVAIL VDDMADTCGT ICHAADKLLS AG ATRVYAI LTHGIFSGPA ISRINNACFE AVVVTNTIPQ EDKMKHCSKI QVIDISMILA EAIRRTHNGE SVSYLFSHVP L UniProtKB: Ribose-phosphate pyrophosphokinase 1 |
-Macromolecule #2: 1-O-pyrophosphono-5-O-phosphono-alpha-D-ribofuranose
Macromolecule | Name: 1-O-pyrophosphono-5-O-phosphono-alpha-D-ribofuranose / type: ligand / ID: 2 / Number of copies: 6 / Formula: PRP |
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Molecular weight | Theoretical: 390.07 Da |
Chemical component information | ![]() ChemComp-PRP: |
-Macromolecule #3: PHOSPHATE ION
Macromolecule | Name: PHOSPHATE ION / type: ligand / ID: 3 / Number of copies: 6 / Formula: PO4 |
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Molecular weight | Theoretical: 94.971 Da |
Chemical component information | ![]() ChemComp-PO4: |
-Macromolecule #4: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 4 / Number of copies: 12 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 12 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | filament |
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Sample preparation
Buffer | pH: 7.6 |
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Grid | Model: C-flat / Material: COPPER / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Instrument: HOMEMADE PLUNGER |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 90.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.75 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Applied symmetry - Point group: D3 (2x3 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 2.4 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: PHENIX (ver. 1.18) / Number images used: 172002 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1) |
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
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Output model | ![]() PDB-8dbl: |