[English] 日本語
![](img/lk-miru.gif)
- EMDB-27288: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer with resolved c... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Human PRPS1 with Phosphate, ATP, and R5P; Hexamer with resolved catalytic loops | |||||||||
![]() | Human PRPS1 with Phosphate, ATP, and R5P; Hexamer Centered with resolved catalytic loops | |||||||||
![]() |
| |||||||||
![]() | ![]() ![]() | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Hvorecny KL / Kollman JM | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 13.3 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 15.2 KB 15.2 KB | Display Display | ![]() |
Images | ![]() | 118.5 KB | ||
Filedesc metadata | ![]() | 5 KB | ||
Others | ![]() ![]() | 97.8 MB 97.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8dbcC ![]() 8dbdC ![]() 8dbeC ![]() 8dbfC ![]() 8dbgC ![]() 8dbhC ![]() 8dbiC ![]() 8dbjC ![]() 8dbkC ![]() 8dblC ![]() 8dbmC ![]() 8dbnC ![]() 8dboC C: citing same article ( |
---|
-
Links
EMDB pages | ![]() ![]() |
---|
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Human PRPS1 with Phosphate, ATP, and R5P; Hexamer Centered with resolved catalytic loops | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.827 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer...
File | emd_27288_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Human PRPS1 with Phosphate, ATP, and R5P; Hexamer Centered with resolved catalytic loops half 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Human PRPS1 with Phosphate, ATP, and R5P; Hexamer...
File | emd_27288_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Human PRPS1 with Phosphate, ATP, and R5P; Hexamer Centered with resolved catalytic loops half 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phospha...
Entire | Name: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phosphate, ATP, and R5P; resolved catalytic loops |
---|---|
Components |
|
-Supramolecule #1: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phospha...
Supramolecule | Name: Hexamer of phosphoribosyl pyrophosphate synthetase 1 with phosphate, ATP, and R5P; resolved catalytic loops type: complex / ID: 1 / Parent: 0 / Macromolecule list: all 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. |
---|---|
Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Human Phosphoribosyl Pyrophosphate Synthetase 1
Macromolecule | Name: Human Phosphoribosyl Pyrophosphate Synthetase 1 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MPNIKIFSGS SHQDLSQKIA DRLGLELGKV VTKKFSNQET CVEIGESVRG EDVYIVQSGC GEINDNLME LLIMINACKI ASASRVTAVI PCFPYARQDK KDKSRAPISA KLVANMLSVA G ADHIITMD LHASQIQGFF DIPVDNLYAE PAVLKWIREN ISEWRNCTIV ...String: MPNIKIFSGS SHQDLSQKIA DRLGLELGKV VTKKFSNQET CVEIGESVRG EDVYIVQSGC GEINDNLME LLIMINACKI ASASRVTAVI PCFPYARQDK KDKSRAPISA KLVANMLSVA G ADHIITMD LHASQIQGFF DIPVDNLYAE PAVLKWIREN ISEWRNCTIV SPDAGGAKRV TS IADRLNV DFALIHKERK KANEVDRMVL VGDVKDRVAI LVDDMADTCG TICHAADKLL SAG ATRVYA ILTHGIFSGP AISRINNACF EAVVVTNTIP QEDKMKHCSK IQVIDISMIL AEAI RRTHN GESVSYLFSH VPL |
-Experimental details
-Structure determination
Method | ![]() |
---|---|
![]() | ![]() |
Aggregation state | filament |
-
Sample preparation
Buffer | pH: 7.6 |
---|---|
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 |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 90.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
Startup model | Type of model: NONE |
---|---|
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: RELION (ver. 3.1) |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 2.1 Å / Resolution method: FSC 0.5 CUT-OFF / Software - Name: PHENIX (ver. 1.18) / Number images used: 912162 |
-Atomic model buiding 1
Refinement | Protocol: FLEXIBLE FIT |
---|