3GEN

The 1.6 A crystal structure of human bruton's tyrosine kinase bound to a pyrrolopyrimidine-containing compound

3GEN の概要

• エントリーDOI: 10.2210/pdb3gen/pdb
• 分子名称: Tyrosine-protein kinase BTK, 4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl-cyclopentane (3 entities in total)
• 機能のキーワード: bruton's tyrosine kinase, 4-amino-5-(4-phenoxyphenyl)-5h-pyrrolo[3, 2-d]pyrimidin-7-yl-cyclopentane, tec-family, complex, acetylation, atp-binding, cytoplasm, disease mutation, kinase, membrane, metal-binding, nucleotide-binding, nucleus, phosphoprotein, polymorphism, sh2 domain, sh3 domain, transferase, tyrosine-protein kinase, zinc, zinc-finger
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): Q06187
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33050.92

構造登録者

Marcotte, D.J.,Liu, Y.T.,Arduini, R.M.,Hession, C.A.,Miatkowski, K.,Wildes, C.P.,Cullen, P.F.,Hopkins, B.,Mertsching, E.,Jenkins, T.J.,Romanowski, M.J.,Baker, D.P.,Silvian, L.F. (登録日: 2009-02-25, 公開日: 2010-01-19, 最終更新日: 2024-03-13)

主引用文献

Marcotte, D.J.,Liu, Y.T.,Arduini, R.M.,Hession, C.A.,Miatkowski, K.,Wildes, C.P.,Cullen, P.F.,Hong, V.,Hopkins, B.T.,Mertsching, E.,Jenkins, T.J.,Romanowski, M.J.,Baker, D.P.,Silvian, L.F.
Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases.
Protein Sci., 19:429-439, 2010

PubMed Abstract: Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, plays a crucial role in B-cell maturation and mast cell activation. Although the structures of the unphosphorylated mouse BTK kinase domain and the unphosphorylated and phosphorylated kinase domains of human ITK are known, understanding the kinase selectivity profiles of BTK inhibitors has been hampered by the lack of availability of a high resolution, ligand-bound BTK structure. Here, we report the crystal structures of the human BTK kinase domain bound to either Dasatinib (BMS-354825) at 1.9 A resolution or to 4-amino-5-(4-phenoxyphenyl)-7H-pyrrolospyrimidin- 7-yl-cyclopentane at 1.6 A resolution. This data provides information relevant to the development of small molecule inhibitors targeting BTK and the TEC family of nonreceptor tyrosine kinases. Analysis of the structural differences between the TEC and Src families of kinases near the Trp-Glu-Ile motif in the N-terminal region of the kinase domain suggests a mechanism of regulation of the TEC family members.

PubMed: 20052711
DOI: 10.1002/pro.321

実験手法

X-RAY DIFFRACTION (1.6 Å)