Summary for 9GLR
| Entry DOI | 10.2210/pdb9glr/pdb |
| Related | 1U9A |
| Descriptor | SUMO-conjugating enzyme UBC9 (2 entities in total) |
| Functional Keywords | sumo-1 conjugating enzyme, ubiquitin conjugating protein, sumolyation pathway protein, e2~sumo thioester complex mimic, ligase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 18113.84 |
| Authors | |
| Primary citation | Kumar, M.,Banerjee, S.,Cohen-Kfir, E.,Mitelberg, M.B.,Tiwari, S.,Isupov, M.N.,Dessau, M.,Wiener, R. UFC1 reveals the multifactorial and plastic nature of oxyanion holes in E2 conjugating enzymes. Nat Commun, 16:3912-3912, 2025 Cited by PubMed Abstract: The conjugation of ubiquitin (Ub) or ubiquitin-like proteins (UBL) to target proteins is a crucial post-translational modification that typically involves nucleophilic attack by a lysine on a charged E2 enzyme (E2~Ub/UBL), forming an oxyanion intermediate. Stabilizing this intermediate through an oxyanion hole is vital for progression of the reaction. Still, the mechanism of oxyanion stabilization in E2 enzymes remains unclear, although an asparagine residue in the conserved HPN motif of E2 enzymes was suggested to stabilize the oxyanion intermediate. Here, we study the E2 enzyme UFC1, which presents a TAK rather than an HPN motif. Crystal structures of UFC1 mutants, including one that mimics the oxyanion intermediate, combined with in vitro activity assays, suggest that UFC1 utilizes two distinct types of oxyanion holes, one that stabilizes the oxyanion intermediate during trans-ufmylation mediated by the E3 ligase, and another that stabilizes cis-driven auto-ufmylation. Our findings indicate that oxyanion stabilization is influenced by multiple factors, including C-alpha hydrogen bonding, and is adaptable, enabling different modes of action. PubMed: 40280917DOI: 10.1038/s41467-025-58826-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.72 Å) |
Structure validation
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