4W9E
pVHL:EloB:EloC in complex with (2S,4R)-1-(3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(thiazol-5-yl)benzyl)pyrrolidine-2-carboxamide (ligand 4)
Summary for 4W9E
Entry DOI | 10.2210/pdb4w9e/pdb |
Descriptor | Transcription elongation factor B polypeptide 2, Transcription elongation factor B polypeptide 1, Von Hippel-Lindau disease tumor suppressor, ... (5 entities in total) |
Functional Keywords | protein complex, ubiquitin ligase, hypoxia inducible factor, transcription, ligase |
Biological source | Homo sapiens (Human) More |
Cellular location | Nucleus : Q15370 Q15369 Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337 |
Total number of polymer chains | 12 |
Total formula weight | 168555.13 |
Authors | Gadd, M.S.,Soares, P.,Galdeano, C.,van Molle, I.,Ciulli, A. (deposition date: 2014-08-27, release date: 2014-09-10, Last modification date: 2024-10-23) |
Primary citation | Galdeano, C.,Gadd, M.S.,Soares, P.,Scaffidi, S.,Van Molle, I.,Birced, I.,Hewitt, S.,Dias, D.M.,Ciulli, A. Structure-Guided Design and Optimization of Small Molecules Targeting the Protein-Protein Interaction between the von Hippel-Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities. J.Med.Chem., 57:8657-8663, 2014 Cited by PubMed Abstract: E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities. PubMed: 25166285DOI: 10.1021/jm5011258 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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