ArticleBiomolecules2020
Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Putrescine-bound structure and multi-temperature crystallography provide new insights into ligand binding and conformational heterogeneity in spermidine synthase.Structural dynamics (Melville, N.Y.) · 2026Article
- Article
- Crystallographic fragment screening supports tool compound discovery and reveals conformational flexibility in human deoxyhypusine synthase.Communications chemistry · 2026Article
- Crystal structure of apo human spermidine synthase reveals dynamic rearrangement at the active site.Structural dynamics (Melville, N.Y.) · 2026Article
- Homospermidine synthase evolution and the origin(s) of pyrrolizidine alkaloids in Apocynaceae.American journal of botany · 2025Article
- Development of a reliable, sensitive, and convenient assay for the discovery of new eIF5A hypusination inhibitors.PloS one · 2025Article
- An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors.PLoS neglected tropical diseases · 2024Article
- ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.Cell reports · 2024Article
- Structural Insights into the Mechanisms Underlying Polyaminopathies.International journal of molecular sciences · 2024Review
- Caldomycin, a new guanidopolyamine produced by a novel agmatine homocoupling enzyme involved in homospermidine biosynthesis.Scientific reports · 2024Article
- Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders.Nature communications · 2023Article
- Translation factor accelerating peptide bond formation on the ribosome: EF-P and eIF5A as entropic catalysts and a potential drug targets.BBA advances · 2023Article
- The long road of functional recruitment-The evolution of a gene duplicate to pyrrolizidine alkaloid biosynthesis in the morning glories (Convolvulaceae).Plant direct · 2022Article
- Biogenic Polyamines and Related Metabolites.Biomolecules · 2021Article
- Hypusination, a Metabolic Posttranslational Modification of eIF5A in Plants during Development and Environmental Stress Responses.Plants (Basel, Switzerland) · 2021Review
- Development of an activity assay for characterizing deoxyhypusine synthase and its diverse reaction products.FEBS open bio · 2021Article
- Structural Characterization of Glycerol Kinase from the Thermophilic FungusInternational journal of molecular sciences · 2020Article
- Structural features and development of an assay platform of the parasite target deoxyhypusine synthase of Brugia malayi and Leishmania major.PLoS neglected tropical diseases · 2020Article
- New Series of Potent Allosteric Inhibitors of Deoxyhypusine Synthase.ACS medicinal chemistry letters · 2020Article
- Flexible NADInternational journal of molecular sciences · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Deoxyhypusine synthase (DHS) is a transferase enabling the formation of deoxyhypusine, which is the first, rate-limiting step of a unique post-translational modification: hypusination. DHS catalyses the transfer of a 4-aminobutyl moiety of polyamine spermidine to a specific lysine of eukaryotic translation factor 5A (eIF5A) precursor in a nicotinamide adenine dinucleotide (NAD)-dependent manner. This modification occurs exclusively on one protein, eIF5A, and it is essential for cell proliferation. Malfunctions of the hypusination pathway, including those caused by mutations within the DHS encoding gene, are associated with conditions such as cancer or neurodegeneration. Here, we present a series of high-resolution crystal structures of human DHS. Structures were determined as the apoprotein, as well as ligand-bound states at high-resolutions ranging from 1.41 to 1.69 Å. By solving DHS in complex with its natural substrate spermidine (SPD), we identified the mode of substrate recognition. We also observed that other polyamines, namely spermine (SPM) and putrescine, bind DHS in a similar manner as SPD. Moreover, we performed activity assays showing that SPM could to some extent serve as an alternative DHS substrate. In contrast to previous studies, we demonstrate that no conformational changes occur in the DHS structure upon spermidine-binding. By combining mutagenesis and a light-scattering approach, we show that a conserved "ball-and-chain" motif is indispensable to assembling a functional DHS tetramer. Our study substantially advances our knowledge of the substrate recognition mechanism by DHS and may aid the design of pharmacological compounds for potential applications in cancer therapy.
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