9EYH
Ubiquitin conjugating enzyme Ubc6 UBC domain with isopeptide-linked ubiquitin
This is a non-PDB format compatible entry.
Summary for 9EYH
| Entry DOI | 10.2210/pdb9eyh/pdb |
| Related | 9EN5 9EWP |
| Descriptor | Ubiquitin-conjugating enzyme E2 6, Ubiquitin-40S ribosomal protein S31 (2 entities in total) |
| Functional Keywords | ubiquitin, endoplasmic reticulum associated degradation, transferase |
| Biological source | Saccharomyces cerevisiae (brewer's yeast) More |
| Total number of polymer chains | 4 |
| Total formula weight | 57883.64 |
| Authors | Swarnkar, A.,Stein, A. (deposition date: 2024-04-09, release date: 2024-11-20, Last modification date: 2024-12-25) |
| Primary citation | Swarnkar, A.,Leidner, F.,Rout, A.K.,Ainatzi, S.,Schmidt, C.C.,Becker, S.,Urlaub, H.,Griesinger, C.,Grubmuller, H.,Stein, A. Determinants of chemoselectivity in ubiquitination by the J2 family of ubiquitin-conjugating enzymes. Embo J., 43:6705-6739, 2024 Cited by PubMed Abstract: Ubiquitin-conjugating enzymes (E2) play a crucial role in the attachment of ubiquitin to proteins. Together with ubiquitin ligases (E3), they catalyze the transfer of ubiquitin (Ub) onto lysines with high chemoselectivity. A subfamily of E2s, including yeast Ubc6 and human Ube2J2, also mediates noncanonical modification of serines, but the structural determinants for this chemical versatility remain unknown. Using a combination of X-ray crystallography, molecular dynamics (MD) simulations, and reconstitution approaches, we have uncovered a two-layered mechanism that underlies this unique reactivity. A rearrangement of the Ubc6/Ube2J2 active site enhances the reactivity of the E2-Ub thioester, facilitating attack by weaker nucleophiles. Moreover, a conserved histidine in Ubc6/Ube2J2 activates a substrate serine by general base catalysis. Binding of RING-type E3 ligases further increases the serine selectivity inherent to Ubc6/Ube2J2, via an allosteric mechanism that requires specific positioning of the ubiquitin tail at the E2 active site. Our results elucidate how subtle structural modifications to the highly conserved E2 fold yield distinct enzymatic activity. PubMed: 39533056DOI: 10.1038/s44318-024-00301-3 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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