2PTK

CHICKEN SRC TYROSINE KINASE

2PTK の概要

• エントリーDOI: 10.2210/pdb2ptk/pdb
• 分子名称: TYROSINE-PROTEIN KINASE TRANSFORMING PROTEIN SRC (2 entities in total)
• 機能のキーワード: tyrosine-protein kinase, src, sh2, sh3
• 由来する生物種: Gallus gallus (chicken)
• 細胞内の位置: Cell membrane : P00523
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51733.55

構造登録者

Williams, J.C.,Wierenga, R. (登録日: 1997-06-17, 公開日: 1997-12-24, 最終更新日: 2024-10-16)

主引用文献

Williams, J.C.,Weijland, A.,Gonfloni, S.,Thompson, A.,Courtneidge, S.A.,Superti-Furga, G.,Wierenga, R.K.
The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions
J.Mol.Biol., 274:757-775, 1997

PubMed Abstract: The Src protein tyrosine kinase plays a critical role in a variety of signal transduction pathways. Strict regulation of its activity is necessary for proper signalling. We present here the crystal structure of chicken Src which is phosphorylated at Tyr527 and represents its least active form. Our structure, similar to the recently reported human Hck and Src structures, contains the SH3, SH2 and the kinase domains and the C-terminal regulatory tail but not the N-terminal unique domain. The SH3 domain uses its hydrophobic surface to coordinate the SH2-kinase linker such that residues Gln251 and Leu255 specifically interact with side chains in the beta2-beta3 and the alphaC-beta4 loops of the N-terminal lobe opposite of the kinase active site. This position of the SH3 domain and the coordination of the SH2-kinase linker also optimally places the SH2 domain such that the phosphorylated Tyr527 in the C-terminal tail interacts with the SH2 binding pocket. Analogous to Cdk2 kinase, the position of the Src alphaC-helix in the N-terminal lobe is swung out disrupting the position of the active site residues. Superposition of other protein kinases including human Hck and Src onto chicken Src indicate that the alphaC-helix position is affected by the relative position of the N-terminal lobe with respect to the C-terminal lobe of the kinase and that the presence of the SH3/SH2-kinase linker/N-terminal lobe interactions restricts the kinase lobes and alphaC-helix access to the active conformation. These superpositions also suggest that the highly conserved alphaC-beta4 loop restricts the conformational freedom of the N-terminal lobe by anchoring it to the C-terminal lobe. Finally, based on sequence alignments and conservation of hydrophobic residues in the Src SH2-kinase linker as well as in the alphaC-beta4 and beta2-beta3 loops, we propose that the Src-related kinases, Abl, Btk and Csk, share the same quaternary structure.

PubMed: 9405157
DOI: 10.1006/jmbi.1997.1426

実験手法

X-RAY DIFFRACTION (2.35 Å)