3ZRC
pVHL54-213-EloB-EloC complex (4R)-4-HYDROXY-1-[(3-METHYLISOXAZOL-5-YL)ACETYL]-N-[4-(1,3-OXAZOL-5-YL)BENZYL]-L-PROLINAMIDE bound
Summary for 3ZRC
| Entry DOI | 10.2210/pdb3zrc/pdb |
| Related | 1LM8 1LQB 1VCB 2C9W 2IZV 2XAI 3ZRF 3ZTC 3ZTD 3ZUN |
| 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 | transcription, tumour supressor protein, chronic aneamia tre e3 treatment, e3 ubiquitin ligase |
| Biological source | HOMO SAPIENS More |
| Cellular location | Nucleus (Probable): Q15370 Q15369 Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337 |
| Total number of polymer chains | 12 |
| Total formula weight | 173493.03 |
| Authors | Van Molle, I.,Buckley, D.L.,Crews, C.M.,Ciulli, A. (deposition date: 2011-06-15, release date: 2012-03-07, Last modification date: 2023-12-20) |
| Primary citation | Buckley, D.L.,Van Molle, I.,Gareiss, P.C.,Tae, H.S.,Michel, J.,Noblin, D.J.,Jorgensen, W.L.,Ciulli, A.,Crews, C.M. Targeting the Von Hippel-Lindau E3 Ubiquitin Ligase Using Small Molecules to Disrupt the Vhl/Hif-1Alpha Interaction J.Am.Chem.Soc., 134:4465-, 2012 Cited by PubMed Abstract: E3 ubiquitin ligases, which bind protein targets, leading to their ubiquitination and subsequent degradation, are attractive drug targets due to their exquisite substrate specificity. However, the development of small-molecule inhibitors has proven extraordinarily challenging as modulation of E3 ligase activities requires the targeting of protein-protein interactions. Using rational design, we have generated the first small molecule targeting the von Hippel-Lindau protein (VHL), the substrate recognition subunit of an E3 ligase, and an important target in cancer, chronic anemia, and ischemia. We have also obtained the crystal structure of VHL bound to our most potent inhibitor, confirming that the compound mimics the binding mode of the transcription factor HIF-1α, a substrate of VHL. These results have the potential to guide future development of improved lead compounds as therapeutics for the treatment of chronic anemia and ischemia. PubMed: 22369643DOI: 10.1021/JA209924V PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
Download full validation report
