8put | pdb_00008put
IF5A in complex with Deoxyhypusine synthase
Structural highlights
FunctionDHYS_SULIK Catalyzes the NAD-dependent oxidative cleavage of spermidine and the subsequent transfer of the butylamine moiety of spermidine to the epsilon-amino group of a specific lysine residue of the eIF-5A precursor protein to form the intermediate deoxyhypusine residue. Publication Abstract from PubMedThe 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 A 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. Crystal structure of archaeal IF5A-DHS complex reveals insights into the hypusination mechanism.,D'Agostino M, Simonetti A, Motta S, Wolff P, Romagnoli A, Piccinini A, Spinozzi F, Di Marino D, La Teana A, Ennifar E Structure. 2024 Mar 27:S0969-2126(24)00090-X. doi: 10.1016/j.str.2024.03.008. PMID:38582076[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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