Cover Feature: Ligand‐Induced Conformational Plasticity of the CTLH E3 Ligase Receptor GID4 (ChemMedChem 7/2026)
This study explores the development of high-affinity ligands for GID4 – the substrate receptor for the human CTLH E3 ligase. The cover image depicts the structural plasticity of GID4, highlighting three discrete conformational states—closed, semi-open, and open—induced by specific ligand binding. Through structure-based drug design, it was identified how these ligand-dependent shifts remodel the binding pocket. Analyzing how ligand-GID4 complexes cluster can clarify the links between chemical structure and biological activity, aiding the development of new ligands tailored for targeted protein degradation. More details can be found in the Research Article by Michal J. Walczak and co-workers (DOI: 10.1002/cmdc.202500849).
Authors
- Marta Klejnot
- Monika Cuprych (ORCID: https://orcid.org/0000-0003-0750-0617)
- Karolina Maria Górecka (ORCID: https://orcid.org/0000-0002-9843-3888)
- Anna Szlachcic (ORCID: https://orcid.org/0000-0003-0574-1476)
- Weronika Wanat (ORCID: https://orcid.org/0000-0002-8633-6335)
- Janusz Wiśniewski (ORCID: https://orcid.org/0000-0002-4861-5755)
- Bartosz Woźniak (ORCID: https://orcid.org/0000-0002-7460-3344)
- Daria Kotlarek (ORCID: https://orcid.org/0000-0002-5827-6347)
- Sylvain Cottens
- Iwona Mames (ORCID: https://orcid.org/0000-0002-4495-6069)
- Igor H. Wierzbicki (ORCID: https://orcid.org/0009-0004-1441-3233)
- Tomáš Drmota (ORCID: https://orcid.org/0000-0002-3422-127X)
- Martyna W. Pastok (ORCID: https://orcid.org/0000-0002-0183-6876)
- Kamil Przytulski
- Daria Gajewska
- Michał J. Walczak (ORCID: https://orcid.org/0000-0003-2301-052X)
- Toshimitsu Takagi
- A.P. Mathieu
- Ave Krol
- Aleksandra Podkowka
- Magdalena Sypien
- Kinga Jurczak
- Szymon Faliński
- Alicja N. Skowron
- Emilia Krzywiecka
- Michał Biśta
- Dmitrii Shishov
- Justyna Adamczyk
Institutions
- Capricor Therapeutics (United States) (US)
Publication Details
- Journal
- ChemMedChem
- Published
- 2026-04-14
- DOI
- https://doi.org/10.1002/cmdc.70281
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00