3PWY

Crystal structure of an extender (SPD28345)-modified human PDK1 complex 2

3PWY の概要

• エントリーDOI: 10.2210/pdb3pwy/pdb
• 分子名称: 3-phosphoinositide-dependent protein kinase 1, N-[2-({6-[(2-sulfanylethyl)amino]pyrimidin-4-yl}amino)ethyl]propanamide (2 entities in total)
• 機能のキーワード: kinase, fragment-based drug discovery, tethering with extenders, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: O15530
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35729.13

構造登録者

Elling, R.A.,Penny, D.M.,Simmons, R.L.,Erlanson, D.A.,Romanowski, M.J. (登録日: 2010-12-09, 公開日: 2011-04-20, 最終更新日: 2024-10-09)

主引用文献

Erlanson, D.A.,Arndt, J.W.,Cancilla, M.T.,Cao, K.,Elling, R.A.,English, N.,Friedman, J.,Hansen, S.K.,Hession, C.,Joseph, I.,Kumaravel, G.,Lee, W.C.,Lind, K.E.,McDowell, R.S.,Miatkowski, K.,Nguyen, C.,Nguyen, T.B.,Park, S.,Pathan, N.,Penny, D.M.,Romanowski, M.J.,Scott, D.,Silvian, L.,Simmons, R.L.,Tangonan, B.T.,Yang, W.,Sun, L.
Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.
Bioorg.Med.Chem.Lett., 21:3078-3083, 2011

PubMed Abstract: We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.

PubMed: 21459573
DOI: 10.1016/j.bmcl.2011.03.032

実験手法

X-RAY DIFFRACTION (3.5 Å)