1. Covalent fragment-based ligand screening approaches for identification of novel ubiquitin proteasome system modulators.
- Author
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Rothweiler, Elisabeth M., Brennan, Paul E., and Huber, Kilian V. M.
- Subjects
- *
PROTEASOMES , *UBIQUITIN , *ALLOSTERIC proteins , *KEAP1 (Protein) , *UBIQUITIN-conjugating enzymes , *SMALL molecules - Abstract
Homologous to E6-AP carboxy terminus (HECT) E3 ligases form a covalent E3-Ub intermediate via a cysteine-dependent trans-thiolation reaction before transferring Ub to the substrate. Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity. Keywords: ABPP; chemoproteomics; covalent fragments; E3 ligase; PROTAC; ubiquitin EN ABPP chemoproteomics covalent fragments E3 ligase PROTAC ubiquitin 391 402 12 03/11/22 20220301 NES 220301 Introduction Posttranslational modification of proteins by ubiquitin (Ub) enables eukaryotic cells to alter protein stability, function and interactions ([44]; [93]). In the third step, Ub is transferred to a substrate's lysine residue, usually the -amino group, by interaction with a ubiquitin-protein ligase (E3) resulting in Ub chain formation ([58]). Really interesting new gene (RING) E3 ligases recruit E2-Ub via a zinc-containing RING domain and then proceed to mediate the transfer of Ub to substrates. [Extracted from the article]
- Published
- 2022
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