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- EMDB-24439: HUMAN IMPDH1 TREATED WITH GTP, IMP, AND NAD+; INTERFACE-CENTERED -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24439 | ||||||||||||
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Title | HUMAN IMPDH1 TREATED WITH GTP, IMP, AND NAD+; INTERFACE-CENTERED | ||||||||||||
![]() | HUMAN IMPDH1 TREATED WITH GTP, IMP, AND NAD+ INTERFACE-CENTERED | ||||||||||||
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![]() | METABOLISM / FILAMENT / ALLOSTERY / ADENINE / OXIDOREDUCTASE | ||||||||||||
Function / homology | ![]() Purine ribonucleoside monophosphate biosynthesis / IMP dehydrogenase activity / IMP dehydrogenase / GMP biosynthetic process / Azathioprine ADME / GTP biosynthetic process / azurophil granule lumen / secretory granule lumen / ficolin-1-rich granule lumen / Potential therapeutics for SARS ...Purine ribonucleoside monophosphate biosynthesis / IMP dehydrogenase activity / IMP dehydrogenase / GMP biosynthetic process / Azathioprine ADME / GTP biosynthetic process / azurophil granule lumen / secretory granule lumen / ficolin-1-rich granule lumen / Potential therapeutics for SARS / nucleic acid binding / nucleotide binding / Neutrophil degranulation / DNA binding / RNA binding / extracellular region / identical protein binding / nucleus / metal ion binding / cytosol / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||||||||
![]() | Burrell AL / Kollman JM | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: IMPDH1 retinal variants control filament architecture to tune allosteric regulation. Authors: Anika L Burrell / Chuankai Nie / Meerit Said / Jacqueline C Simonet / David Fernández-Justel / Matthew C Johnson / Joel Quispe / Rubén M Buey / Jeffrey R Peterson / Justin M Kollman / ![]() ![]() Abstract: Inosine-5'-monophosphate dehydrogenase (IMPDH), a key regulatory enzyme in purine nucleotide biosynthesis, dynamically assembles filaments in response to changes in metabolic demand. Humans have two ...Inosine-5'-monophosphate dehydrogenase (IMPDH), a key regulatory enzyme in purine nucleotide biosynthesis, dynamically assembles filaments in response to changes in metabolic demand. Humans have two isoforms: IMPDH2 filaments reduce sensitivity to feedback inhibition, while IMPDH1 assembly remains uncharacterized. IMPDH1 plays a unique role in retinal metabolism, and point mutants cause blindness. Here, in a series of cryogenic-electron microscopy structures we show that human IMPDH1 assembles polymorphic filaments with different assembly interfaces in extended and compressed states. Retina-specific splice variants introduce structural elements that reduce sensitivity to GTP inhibition, including stabilization of the extended filament form. Finally, we show that IMPDH1 disease mutations fall into two classes: one disrupts GTP regulation and the other has no effect on GTP regulation or filament assembly. These findings provide a foundation for understanding the role of IMPDH1 in retinal function and disease and demonstrate the diverse mechanisms by which metabolic enzyme filaments are allosterically regulated. | ||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 115.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.3 KB 11.3 KB | Display Display | ![]() |
Images | ![]() | 134.4 KB | ||
Filedesc metadata | ![]() | 5.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7rfeMC ![]() 7rerC ![]() 7resC ![]() 7rffC ![]() 7rfgC ![]() 7rfhC ![]() 7rfiC ![]() 7rgdC ![]() 7rgiC ![]() 7rglC ![]() 7rgmC ![]() 7rgqC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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 IMPDH1 TREATED WITH GTP, IMP, AND NAD+ INTERFACE-CENTERED | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.05 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Assembly interface of IMPDH1 filament bound to ATP, IMP, NAD+
Entire | Name: Assembly interface of IMPDH1 filament bound to ATP, IMP, NAD+ |
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Components |
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-Supramolecule #1: Assembly interface of IMPDH1 filament bound to ATP, IMP, NAD+
Supramolecule | Name: Assembly interface of IMPDH1 filament bound to ATP, IMP, NAD+ type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 55405 MDa |
-Macromolecule #1: Inosine-5'-monophosphate dehydrogenase 1
Macromolecule | Name: Inosine-5'-monophosphate dehydrogenase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO / EC number: IMP dehydrogenase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 54.461527 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GYVPEDGLTA QQLFASADGL TYNDFLILPG FIDFIADEVD LTSALTRKIT LKTPLISSPM DTVTEADMAI AMALMGGIGF IHHNCTPEF QANEVRKVKK FEQGFITDPV VLSPSHTVGD VLEAKMRHGF SGIPITETGT MGSKLVGIVT SRDIDFLAEK D HTTLLSEV ...String: GYVPEDGLTA QQLFASADGL TYNDFLILPG FIDFIADEVD LTSALTRKIT LKTPLISSPM DTVTEADMAI AMALMGGIGF IHHNCTPEF QANEVRKVKK FEQGFITDPV VLSPSHTVGD VLEAKMRHGF SGIPITETGT MGSKLVGIVT SRDIDFLAEK D HTTLLSEV MTPRIELVVA PAGVTLKEAN EILQRSKKGK LPIVNDCDEL VAIIARTDLK KNRDYPLASK DSQKQLLCGA AV GTREDDK YRLDLLTQAG VDVIVLDSSQ GNSVYQIAMV HYIKQKYPHL QVIGGNVVTA AQAKNLIDAG VDGLRVGMGC GSI CITQEV MACGRPQGTA VYKVAEYARR FGVPIIADGG IQTVGHVVKA LALGASTVMM GSLLAATTEA PGEYFFSDGV RLKK YRGMG SLDAMEKSSS SQKRYFSEGD KVKIAQGVSG SIQDKGSIQK FVPYLIAGIQ HGCQDIGARS LSVLRSMMYS GELKF EKRT MSAQIEGGVH GLHSYEKRLY UniProtKB: Inosine-5'-monophosphate dehydrogenase 1 |
-Macromolecule #2: GUANOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: GUANOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 16 / Formula: GTP |
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Molecular weight | Theoretical: 523.18 Da |
Chemical component information | ![]() ChemComp-GTP: |
-Macromolecule #3: ADENOSINE-5'-TRIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-TRIPHOSPHATE / type: ligand / ID: 3 / Number of copies: 8 / Formula: ATP |
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Molecular weight | Theoretical: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-Macromolecule #4: INOSINIC ACID
Macromolecule | Name: INOSINIC ACID / type: ligand / ID: 4 / Number of copies: 8 / Formula: IMP |
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Molecular weight | Theoretical: 348.206 Da |
Chemical component information | ![]() ChemComp-I: |
-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 |
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Vitrification | Cryogen name: ETHANE |
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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) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: EMDB MAP |
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Final reconstruction | Applied symmetry - Point group: D4 (2x4 fold dihedral) / Resolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 42500 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |