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- PDB-7a6s: Crystal Structure of Asn173Ser variant of Human Deoxyhypusine Synthase -
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Open data
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Basic information
Entry | Database: PDB / ID: 7a6s | ||||||||||||
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Title | Crystal Structure of Asn173Ser variant of Human Deoxyhypusine Synthase | ||||||||||||
![]() | Deoxyhypusine synthase | ||||||||||||
![]() | TRANSFERASE / deoxyhypusine synthase / hypusination / hypusine / translation / neurodegeneration / spermidine dhps deficiency | ||||||||||||
Function / homology | ![]() deoxyhypusine synthase / Hypusine synthesis from eIF5A-lysine / peptidyl-lysine modification to peptidyl-hypusine / deoxyhypusine synthase activity / spermidine metabolic process / spermidine catabolic process / positive regulation of T cell proliferation / glucose homeostasis / translation / positive regulation of cell population proliferation ...deoxyhypusine synthase / Hypusine synthesis from eIF5A-lysine / peptidyl-lysine modification to peptidyl-hypusine / deoxyhypusine synthase activity / spermidine metabolic process / spermidine catabolic process / positive regulation of T cell proliferation / glucose homeostasis / translation / positive regulation of cell population proliferation / identical protein binding / cytosol / cytoplasm Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ![]() ![]() ![]() | ||||||||||||
![]() | Wator, E. / Wilk, P. / Grudnik, P. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders. Authors: Elżbieta Wątor / Piotr Wilk / Artur Biela / Michał Rawski / Krzysztof M Zak / Wieland Steinchen / Gert Bange / Sebastian Glatt / Przemysław Grudnik / ![]() ![]() Abstract: Hypusination is a unique post-translational modification of the eukaryotic translation factor 5A (eIF5A) that is essential for overcoming ribosome stalling at polyproline sequence stretches. The ...Hypusination is a unique post-translational modification of the eukaryotic translation factor 5A (eIF5A) that is essential for overcoming ribosome stalling at polyproline sequence stretches. The initial step of hypusination, the formation of deoxyhypusine, is catalyzed by deoxyhypusine synthase (DHS), however, the molecular details of the DHS-mediated reaction remained elusive. Recently, patient-derived variants of DHS and eIF5A have been linked to rare neurodevelopmental disorders. Here, we present the cryo-EM structure of the human eIF5A-DHS complex at 2.8 Å resolution and a crystal structure of DHS trapped in the key reaction transition state. Furthermore, we show that disease-associated DHS variants influence the complex formation and hypusination efficiency. Hence, our work dissects the molecular details of the deoxyhypusine synthesis reaction and reveals how clinically-relevant mutations affect this crucial cellular process. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 418.7 KB | Display | ![]() |
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PDB format | ![]() | 350.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 7a6tC ![]() 8a0eC ![]() 8a0fC ![]() 8a0gC ![]() 6xxjS S: Starting model for refinement C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components on special symmetry positions |
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Components
#1: Protein | Mass: 41017.477 Da / Num. of mol.: 2 / Mutation: N173S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-EDO / #3: Chemical | #4: Chemical | ChemComp-OXM / | #5: Water | ChemComp-HOH / | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.12 Å3/Da / Density % sol: 60.63 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop Details: 0.025-0.125 mM carboxylic acid mix, 30-60% precipitant mix (MPD, PEG 3350, PEG 1000), 100 mM Tris-Bicine pH = 8.5 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Apr 14, 2020 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9184 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 1.75→46.03 Å / Num. obs: 200356 / % possible obs: 99.9 % / Redundancy: 5.241 % / Biso Wilson estimate: 38.039 Å2 / CC1/2: 0.996 / Rmerge(I) obs: 0.12 / Rrim(I) all: 0.133 / Χ2: 1.115 / Net I/σ(I): 7.2 / Num. measured all: 1050137 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 6XXJ Resolution: 1.75→46.03 Å / SU ML: 0.29 / Cross valid method: THROUGHOUT / σ(F): 1.15 / Phase error: 24.86 / Stereochemistry target values: ML
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 263.09 Å2 / Biso mean: 50.8976 Å2 / Biso min: 22.35 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 1.75→46.03 Å
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15
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