4LGG

Structure of 3MB-PP1 bound to analog-sensitive Src kinase

4LGG の概要

• エントリーDOI: 10.2210/pdb4lgg/pdb
• 関連するPDBエントリー: 4LGH
• 分子名称: Proto-oncogene tyrosine-protein kinase Src, 1-tert-butyl-3-(3-methylbenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (3 entities in total)
• 機能のキーワード: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Gallus gallus (bantam,chickens)
• 細胞内の位置: Cell membrane : P00523
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62423.99

構造登録者

Lopez, M.S.,Dar, A.C.,Shokat, K.M. (登録日: 2013-06-27, 公開日: 2013-08-07, 最終更新日: 2024-02-28)

主引用文献

Zhang, C.,Lopez, M.S.,Dar, A.C.,Ladow, E.,Finkbeiner, S.,Yun, C.H.,Eck, M.J.,Shokat, K.M.
Structure-guided inhibitor design expands the scope of analog-sensitive kinase technology.
Acs Chem.Biol., 8:1931-1938, 2013

PubMed Abstract: Engineered analog-sensitive (AS) protein kinases have emerged as powerful tools for dissecting phospho-signaling pathways, for elucidating the cellular function of individual kinases, and for deciphering unanticipated effects of clinical therapeutics. A crucial and necessary feature of this technology is a bioorthogonal small molecule that is innocuous toward native cellular systems but potently inhibits the engineered kinase. In order to generalize this method, we sought a molecule capable of targeting divergent AS-kinases. Here we employ X-ray crystallography and medicinal chemistry to unravel the mechanism of current inhibitors and use these insights to design the most potent, selective, and general AS-kinase inhibitors reported to date. We use large-scale kinase inhibitor profiling to characterize the selectivity of these molecules as well as examine the consequences of potential off-target effects in chemical genetic experiments. The molecules reported here will serve as powerful tools in efforts to extend AS-kinase technology to the entire kinome and the principles discovered may help in the design of other engineered enzyme/ligand pairs.

PubMed: 23841803
DOI: 10.1021/cb400376p

実験手法

X-RAY DIFFRACTION (2.41 Å)