4AJY

von Hippel-Lindau protein-ElonginB-ElonginC complex, bound to Hif1- alpha peptide

4AJY の概要

• エントリーDOI: 10.2210/pdb4ajy/pdb
• 関連するPDBエントリー: 1D7G 1H2K 1H2L 1H2M 1L3E 1L8C 1LM8 1LQB 1VCB 2C9W 2IZV 2XAI 3ZRC 3ZRF 3ZTC 3ZTD 3ZUN
• 分子名称: TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 2, TRANSCRIPTION ELONGATION FACTOR B POLYPEPTIDE 1, HYPOXIA-INDUCIBLE FACTOR 1-ALPHA, ... (6 entities in total)
• 機能のキーワード: e3 ubiquitin ligase, transcription factor, hypoxic signaling, transcription
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Nucleus (Probable): Q15370 Q15369; Cytoplasm: Q16665; Isoform 1: Cytoplasm. Isoform 3: Cytoplasm: P40337
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 45315.39

構造登録者

Van Molle, I.,Thomann, A.,Buckley, D.L.,So, E.C.,Lang, S.,Crews, C.M.,Ciulli, A. (登録日: 2012-02-21, 公開日: 2012-11-14, 最終更新日: 2023-12-20)

主引用文献

Van Molle, I.,Thomann, A.,Buckley, D.L.,So, E.C.,Lang, S.,Crews, C.M.,Ciulli, A.
Dissecting Fragment-Based Lead Discovery at the Von Hippel-Lindau Protein:Hypoxia Inducible Factor 1Alpha Protein-Protein Interface.
Chem.Biol., 19:1300-, 2012

PubMed Abstract: Fragment screening is widely used to identify attractive starting points for drug design. However, its potential and limitations to assess the tractability of often challenging protein:protein interfaces have been underexplored. Here, we address this question by means of a systematic deconstruction of lead-like inhibitors of the pVHL:HIF-1α interaction into their component fragments. Using biophysical techniques commonly employed for screening, we could only detect binding of fragments that violate the Rule of Three, are more complex than those typically screened against classical druggable targets, and occupy two adjacent binding subsites at the interface rather than just one. Analyses based on ligand and group lipophilicity efficiency of anchored fragments were applied to dissect the individual subsites and probe for binding hot spots. The implications of our findings for targeting protein interfaces by fragment-based approaches are discussed.

PubMed: 23102223
DOI: 10.1016/J.CHEMBIOL.2012.08.015

実験手法

X-RAY DIFFRACTION (1.73 Å)