3CQW

Crystal Structure of Akt-1 complexed with substrate peptide and inhibitor

3CQW の概要

• エントリーDOI: 10.2210/pdb3cqw/pdb
• 関連するPDBエントリー: 3CQU
• 分子名称: RAC-alpha serine/threonine-protein kinase, Glycogen synthase kinase-3 beta, MANGANESE (II) ION, ... (5 entities in total)
• 機能のキーワード: kinase, apoptosis, atp-binding, carbohydrate metabolism, cytoplasm, glucose metabolism, glycogen biosynthesis, glycogen metabolism, membrane, nucleotide-binding, nucleus, phosphoprotein, serine/threonine-protein kinase, sugar transport, transferase, translation regulation, transport, alternative splicing, wnt signaling pathway
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: P31749 P49841
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41060.96

構造登録者

Pandit, J. (登録日: 2008-04-03, 公開日: 2008-05-27, 最終更新日: 2024-11-20)

主引用文献

Lippa, B.,Pan, G.,Corbett, M.,Li, C.,Kauffman, G.S.,Pandit, J.,Robinson, S.,Wei, L.,Kozina, E.,Marr, E.S.,Borzillo, G.,Knauth, E.,Barbacci-Tobin, E.G.,Vincent, P.,Troutman, M.,Baker, D.,Rajamohan, F.,Kakar, S.,Clark, T.,Morris, J.
Synthesis and structure based optimization of novel Akt inhibitors
Bioorg.Med.Chem.Lett., 18:3359-3363, 2008

PubMed Abstract: Based on a high throughput screening hit, pyrrolopyrimidine inhibitors of the Akt kinase are explored. X-ray co-crystal structures of two lead series results in the understanding of key binding interactions, the design of new lead series, and enhanced potency. The syntheses of these series and their biological activities are described. Spiroindoline 13j is found to have an Akt1 kinase IC(50) of 2.4+/-0.6 nM, Akt cell potency of 50+/-19 nM, and provides 68% inhibition of tumor growth in a mouse xenograft model (50 mg/kg, qd, po).

PubMed: 18456494
DOI: 10.1016/j.bmcl.2008.04.034

実験手法

X-RAY DIFFRACTION (2 Å)