9RSD
Ternary complex of a charged molecular glue degrader ZZ1-SO2H, BRD4(BD1) neosubstrate, and the CTLH E3 ligase receptor module YPEL5-WDR26
This is a non-PDB format compatible entry.
Summary for 9RSD
| Entry DOI | 10.2210/pdb9rsd/pdb |
| Related | 9RSC |
| EMDB information | 54215 54216 |
| Descriptor | WD repeat-containing protein 26, Protein yippee-like 5, Bromodomain-containing protein 4, ... (6 entities in total) |
| Functional Keywords | e3 ubiquitin ligase, ctlh, gid, ypel5, molecular glue degrader, targeted protein degradation, ligase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 171003.02 |
| Authors | Chrustowicz, J.,Schulman, B.A. (deposition date: 2025-07-01, release date: 2026-04-08, Last modification date: 2026-04-29) |
| Primary citation | Zhuang, Z.,Byun, W.S.,Chrustowicz, J.,Kozicka, Z.,Li, V.L.,Abeja, D.M.,Donovan, K.A.,Sepic, S.,You, I.,Slabicki, M.,Fischer, E.S.,Hinshaw, S.M.,Ebert, B.L.,Schulman, B.A.,Gray, N.S. Charged molecular glue discovery enabled by targeted degron display. Nat.Chem.Biol., 2026 Cited by PubMed Abstract: Small molecules that induce protein interactions hold tremendous potential as new medicines, probes for molecular pathways and tools for agriculture. Explosive growth of targeted protein degradation drug development has spurred renewed interest in proximity-inducing molecules, especially molecular glue degraders (MGDs). These compounds catalyze the destruction of disease-causing proteins by reshaping protein surfaces and promoting cooperative binding between ubiquitylating enzymes and target proteins. MGD discovery for predefined targets is a major challenge in contemporary drug discovery. Here, we solve this important chemical challenge through 'chemocentric' MGD discovery of ZZ1, a BET-family protein degrader and a prodrug of a negatively charged glue. ZZ1 activation unmasks a sulfinic acid that binds the modular CTLH ubiquitin ligase complex through a basic pocket in its YPEL5 subunit. These findings demonstrate a previously unrecognized capacity of YPEL5 to recruit CTLH substrates and enable the discovery of MGDs for exceedingly common acidic and basic degrons. PubMed: 41942733DOI: 10.1038/s41589-026-02182-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.38 Å) |
Structure validation
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