8PUT
IF5A in complex with Deoxyhypusine synthase
Summary for 8PUT
| Entry DOI | 10.2210/pdb8put/pdb |
| Descriptor | Probable deoxyhypusine synthase, Translation initiation factor 5A, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total) |
| Functional Keywords | lysine modification, hypusine, translation, eif5a |
| Biological source | Sulfolobus islandicus More |
| Total number of polymer chains | 8 |
| Total formula weight | 201261.03 |
| Authors | Ennifar, E.,D'agostino, M. (deposition date: 2023-07-17, release date: 2024-07-03, Last modification date: 2024-07-24) |
| Primary citation | D'Agostino, M.,Simonetti, A.,Motta, S.,Wolff, P.,Romagnoli, A.,Piccinini, A.,Spinozzi, F.,Di Marino, D.,La Teana, A.,Ennifar, E. Crystal structure of archaeal IF5A-DHS complex reveals insights into the hypusination mechanism. Structure, 32:878-, 2024 Cited by PubMed Abstract: The translation factor IF5A is highly conserved in Eukarya and Archaea and undergoes a unique post-translational hypusine modification by the deoxyhypusine synthase (DHS) enzyme. DHS transfers the butylamine moiety from spermidine to IF5A using NAD as a cofactor, forming a deoxyhypusine intermediate. IF5A is a key player in protein synthesis, preventing ribosome stalling in proline-rich sequences during translation elongation and facilitating translation elongation and termination. Additionally, human eIF5A participates in various essential cellular processes and contributes to cancer metastasis, with inhibiting hypusination showing anti-proliferative effects. The hypusination pathway of IF5A is therefore an attractive new therapeutic target. We elucidated the 2.0 Å X-ray crystal structure of the archaeal DHS-IF5A complex, revealing hetero-octameric architecture and providing a detailed view of the complex active site including the hypusination loop. This structure, along with biophysical data and molecular dynamics simulations, provides new insights into the catalytic mechanism of the hypusination reaction. PubMed: 38582076DOI: 10.1016/j.str.2024.03.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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