9ido | pdb_00009ido

Human Deoxyhypusine Synthase Fragment Screening Campaign - UNLand VT00188

spinqualitylabelsall models 9ido, resolution 1.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ido is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.39Å Ligands: A1I2R, CSS, MRD, NAD Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DHYS_HUMAN 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 PubMed Deoxyhypusine synthase (DHS) catalyzes the rate-limiting step of hypusination, a unique post-translational modification of eukaryotic translation factor 5 A (eIF5A). While DHS activity plays a critical role in both normal cellular processes and disease development, the lack of specific molecular tools has hindered detailed studies of this enzyme and the hypusination pathway in general. Existing inhibitors, such as polyamine analogs, suffer from limited specificity and versatility. In this study, we utilized crystallographic fragment screening (CFS) to identify potential DHS inhibitors and explore novel applications of this approach. With an unprecedented hit rate of 39%, we identified fragment clusters binding at key sites, including the active site entrance, the tetramer interface, the regulatory ball-and-chain motif, and potentially allosteric regions on the enzyme's surface. Notably, we discovered a covalent modifier that targets the catalytic lysine residue in an oxidoreductase reaction-specific manner, as well as fragments that induce significant structural rearrangements of crucial regulatory elements. Our findings establish a framework for extending CFS beyond traditional inhibitor discovery, demonstrating its utility in probing protein dynamics, identifying novel binding pockets, and investigating regulatory mechanisms. These results offer new insights into DHS function, hypusination dynamics, and the broader methodological advancements that CFS contributes to structural biology and protein regulation research. Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase.,Wilk P, Wator-Wilk E, Muszak D, Kochanowski P, Krojer T, Grudnik P Commun Chem. 2026 Jan 17;9(1):66. doi: 10.1038/s42004-026-01897-9. PMID:41548022 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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