3ZRF

pVHL54-213-EloB-EloC complex_apo

3ZRF の概要

• エントリーDOI: 10.2210/pdb3zrf/pdb
• 関連するPDBエントリー: 1LM8 1LQB 1VCB 2C9W 2IZV 2XAI 3ZRC
• 分子名称: TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 2, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, VON HIPPEL-LINDAU DISEASE TUMOR SUPPRESSOR,, ... (4 entities in total)
• 機能のキーワード: transcription, tumour supressor protein, chronic aneamia treatment, e3 ubiquitin ligase
• 由来する生物種: HOMO SAPIENS; 詳細
• 細胞内の位置: Nucleus (Probable): Q15370 Q15369; Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 171851.34

構造登録者

Van Molle, I.,Buckley, D.L.,Crews, C.M.,Ciulli, A. (登録日: 2011-06-16, 公開日: 2012-03-07, 最終更新日: 2023-12-20)

主引用文献

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

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: 22369643
DOI: 10.1021/JA209924V

実験手法

X-RAY DIFFRACTION (2.8 Å)