9GD6
NME1 94-Phosphoserine
Summary for 9GD6
| Entry DOI | 10.2210/pdb9gd6/pdb |
| Related | 9GD8 9GD9 |
| EMDB information | 51248 51250 51251 |
| Descriptor | Nucleoside diphosphate kinase A (1 entity in total) |
| Functional Keywords | nucleotide kinase, post-translational modification, phosphorylation, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 6 |
| Total formula weight | 109180.51 |
| Authors | Roderer, D.,Schoepf, F.,Fiedler, D.,Celik, A. (deposition date: 2024-08-05, release date: 2025-06-11, Last modification date: 2025-11-12) |
| Primary citation | Celik, A.,Schopf, F.,Stieger, C.E.,Lampe, S.,Hanf, B.,Morgan, J.A.M.,Ruwolt, M.,Liu, F.,Hackenberger, C.P.R.,Roderer, D.,Fiedler, D. Nucleoside diphosphate kinase A (NME1) catalyses its own oligophosphorylation. Nat.Chem., 17:1757-1767, 2025 Cited by PubMed Abstract: Protein phosphorylation is a central signalling mechanism in eukaryotic cells. The scope of this post-translational modification includes protein pyro- and polyphosphorylation. Here we report the discovery of another mode of phosphorylation: protein oligophosphorylation. Using site-specifically phosphorylated and pyrophosphorylated nucleoside diphosphate kinase A (NME1), the effects of these modifications on enzyme activity were investigated. Phosphorylation, and more so pyrophosphorylation, on Thr94 reduced the nucleoside diphosphate kinase activity. Nevertheless, both phosphoprotein and pyrophosphoprotein catalysed their own oligophosphorylation-up to the formation of a hexaphosphate chain-using ATP as a cofactor. Oligophosphorylation was critically dependent on the catalytic histidine residue His118, and cryogenic electron microscopy analysis of the modified proteins suggests an intramolecular phosphoryl transfer mechanism. Oligophosphorylation of NME1 in biochemical samples, and in cell lysates, was further confirmed using mass spectrometry, and was found to promote a new set of protein interactions. Our results highlight the complex nature of phosphoregulation, and the methods described here provide the opportunity to investigate the impact of this unusual modification in the future. PubMed: 40835738DOI: 10.1038/s41557-025-01915-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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