3SXR

Crystal structure of BMX non-receptor tyrosine kinase complex with dasatinib

3SXR の概要

• エントリーDOI: 10.2210/pdb3sxr/pdb
• 関連するPDBエントリー: 3SXS
• 分子名称: Cytoplasmic tyrosine-protein kinase BMX, N-(2-CHLORO-6-METHYLPHENYL)-2-({6-[4-(2-HYDROXYETHYL)PIPERAZIN-1-YL]-2-METHYLPYRIMIDIN-4-YL}AMINO)-1,3-THIAZOLE-5-CARBOXAMIDE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P51813
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63684.26

構造登録者

Sack, J.,Muckelbauer, J. (登録日: 2011-07-15, 公開日: 2011-09-21, 最終更新日: 2024-02-28)

主引用文献

Muckelbauer, J.,Sack, J.S.,Ahmed, N.,Burke, J.,Chang, C.Y.,Gao, M.,Tino, J.,Xie, D.,Tebben, A.J.
X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family kinase.
Chem.Biol.Drug Des., 78:739-748, 2011

PubMed Abstract: Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 Å resolution and PP2 at 1.9 Å resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-ordered protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors.

PubMed: 21883956
DOI: 10.1111/j.1747-0285.2011.01230.x

実験手法

X-RAY DIFFRACTION (2.4 Å)