9pxp
Fem-1 homolog B (FEM1B) in complex with VU0416476
Structural highlights
FunctionFEM1B_HUMAN Component of an E3 ubiquitin-protein ligase complex, in which it may act as a substrate recognition subunit. Involved in apoptosis by acting as a death receptor-associated protein that mediates apoptosis. Also involved in glucose homeostasis in pancreatic islet. Functions as an adapter/mediator in replication stress-induced signaling that leads to the activation of CHEK1.[1] [2] Publication Abstract from PubMedTargeted protein degradation using PROTACs (PROteolysis TArgeting Chimeras) has emerged as a transformative therapeutic strategy, largely relying on a small number of E3 ubiquitin ligases such as CRBN and VHL. However, resistance, toxicity, and poor oral bioavailability limit the utility of PROTACs and highlight the need to expand the E3 ligase toolbox. Fem-1 homolog B (FEM1B) is a lesser-known E3 ligase that offers a promising alternative due to its broad expression and ability to recognize diverse degron motifs. Here, we describe the development of a stable construct of FEM1B, the results of a protein-observed NMR-based fragment screen using this construct, and the X-ray structures of some of the fragment hits when bound to the protein. From these results, new PROTACs utilizing FEM1B as the E3 ligase may be discovered, providing an alternative E3 ligase for targeted protein degradation. Nuclear Magnetic Resonance-based fragment screen of the E3 ligase Fem-1 homolog B.,Katinas JM, Amporndanai K, Taylor AJ, Rose KL, Gareiss PC, Crespo RA, Phan J, Waterson AG, Fesik SW Protein Sci. 2025 Dec;34(12):e70365. doi: 10.1002/pro.70365. PMID:41229306[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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