5JCT

Crystal Structure of Human Pirin in complex with a Chemical Probe pyrrolidine 24

5JCT の概要

• エントリーDOI: 10.2210/pdb5jct/pdb
• 分子名称: Pirin, FE (III) ION, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: cupin, beta-barrel fold, inhibitor, complex, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus : O00625
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35185.60

構造登録者

Ali, S.,van Montfort, R. (登録日: 2016-04-15, 公開日: 2017-01-11, 最終更新日: 2024-01-10)

主引用文献

Cheeseman, M.D.,Chessum, N.E.,Rye, C.S.,Pasqua, A.E.,Tucker, M.J.,Wilding, B.,Evans, L.E.,Lepri, S.,Richards, M.,Sharp, S.Y.,Ali, S.,Rowlands, M.,O'Fee, L.,Miah, A.,Hayes, A.,Henley, A.T.,Powers, M.,Te Poele, R.,De Billy, E.,Pellegrino, L.,Raynaud, F.,Burke, R.,van Montfort, R.L.,Eccles, S.A.,Workman, P.,Jones, K.
Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen.
J. Med. Chem., 60:180-201, 2017

PubMed Abstract: Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell-based SAR and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography.

PubMed: 28004573
DOI: 10.1021/acs.jmedchem.6b01055

実験手法

X-RAY DIFFRACTION (1.73 Å)