6OP96OP9 の概要
| エントリーDOI | 10.2210/pdb6op9/pdb |
| 分子名称 | Receptor tyrosine-protein kinase erbB-3, 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile (3 entities in total) |
| 機能のキーワード | receptor tyrosine kinase, pseudokinase, bosutinib, membrane, signaling protein, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| 由来する生物種 | Homo sapiens (Human) |
| タンパク質・核酸の鎖数 | 1 |
| 化学式量合計 | 37472.37 |
| 構造登録者 | |
| 主引用文献 | Campbell, M.R.,Ruiz-Saenz, A.,Peterson, E.,Agnew, C.,Ayaz, P.,Garfinkle, S.,Littlefield, P.,Steri, V.,Oeffinger, J.,Sampang, M.,Shan, Y.,Shaw, D.E.,Jura, N.,Moasser, M.M. Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers. Cell Rep, 38:110291-110291, 2022 Cited by PubMed Abstract: Effective inactivation of the HER2-HER3 tumor driver has remained elusive because of the challenging attributes of the pseudokinase HER3. We report a structure-function study of constitutive HER2-HER3 signaling to identify opportunities for targeting. The allosteric activation of the HER2 kinase domain (KD) by the HER3 KD is required for tumorigenic signaling and can potentially be targeted by allosteric inhibitors. ATP binding within the catalytically inactive HER3 KD provides structural rigidity that is important for signaling, but this is mimicked, not opposed, by small molecule ATP analogs, reported here in a bosutinib-bound crystal structure. Mutational disruption of ATP binding and molecular dynamics simulation of the apo KD of HER3 identify a conformational coupling of the ATP pocket with a hydrophobic AP-2 pocket, analogous to EGFR, that is critical for tumorigenic signaling and feasible for targeting. The value of these potential target sites is confirmed in tumor growth assays using gene replacement techniques. PubMed: 35108525DOI: 10.1016/j.celrep.2021.110291 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.501 Å) |
構造検証レポート
検証レポート(詳細版)
をダウンロード
をダウンロード
