2XBA

Structure of Human Anaplastic Lymphoma Kinase in complex with PHA- E429

2XBA の概要

• エントリーDOI: 10.2210/pdb2xba/pdb
• 関連するPDBエントリー: 2XB7
• 分子名称: ALK TYROSINE KINASE RECEPTOR, 5-[(2R)-2-hydroxy-2-phenylacetyl]-3-({[4-(4-methylpiperazin-1-yl)phenyl]carbonyl}amino)-1,6-dihydropyrrolo[3,4-c]pyrazol-5-ium (3 entities in total)
• 機能のキーワード: atp-binding, receptor, transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q9UM73
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35794.14

構造登録者

Bossi, R.T.,Saccardo, M.B.,Ardini, E.,Menichincheri, M.,Rusconi, L.,Magnaghi, P.,Orsini, P.,Fogliatto, G.,Bertrand, J.A. (登録日: 2010-04-08, 公開日: 2010-07-28, 最終更新日: 2024-05-01)

主引用文献

Bossi, R.T.,Saccardo, M.B.,Ardini, E.,Menichincheri, M.,Rusconi, L.,Magnaghi, P.,Orsini, P.,Avanzi, N.,Borgia, A.L.,Nesi, M.,Bandiera, T.,Fogliatto, G.,Bertrand, J.A.
Crystal Structures of Anaplastic Lymphoma Kinase in Complex with ATP Competitive Inhibitors.
Biochemistry, 49:6813-, 2010

PubMed Abstract: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the development of several human cancers and, as a result, is a recognized target for the development of small-molecule inhibitors for the treatment of ALK-positive malignancies. Here, we present the crystal structures of the unphosphorylated human ALK kinase domain in complex with the ATP competitive ligands PHA-E429 and NVP-TAE684. Analysis of these structures provides valuable information concerning the specific characteristics of the ALK active site as well as giving indications about how to obtain selective ALK inhibitors. In addition, the ALK-KD-PHA-E429 structure led to the identification of a potential regulatory mechanism involving a link made between a short helical segment immediately following the DFG motif and an N-terminal two-stranded beta-sheet. Finally, mapping of the activating mutations associated with neuroblastoma onto our structures may explain the roles these residues have in the activation process.

PubMed: 20695522
DOI: 10.1021/BI1005514

実験手法

X-RAY DIFFRACTION (1.95 Å)