PDBsum entry 2ptk

Tyrosine-protein kinase

PDB id: 2ptk

Contents

Protein chain

426 a.a. *

Waters ×271

* Residue conservation analysis

PDB id:

2ptk

Name:

Tyrosine-protein kinase

Title:

Chicken src tyrosine kinase

Structure:

Tyrosine-protein kinase transforming protein src. Chain: a. Fragment: sh3/sh2/kinasE/C-terminal tail. Synonym: src. Engineered: yes. Other_details: inactive form, phosphorylated at tyr 527

Source:

Gallus gallus. Chicken. Organism_taxid: 9031

Resolution:

2.35Å R-factor: 0.204 R-free: 0.292

Authors:

J.C.Williams,R.Wierenga

Key ref:

J.C.Williams et al. (1997). 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. PubMed id: 9405157 DOI: 10.1006/jmbi.1997.1426

Date:

17-Jun-97 Release date: 24-Dec-97

Protein chain

P00523  (SRC_CHICK) -  Proto-oncogene tyrosine-protein kinase Src from Gallus gallus

Seq: 533 a.a.

Struc: 426 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.10.2 - non-specific protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1006/jmbi.1997.1426

J Mol Biol 274:757-775 (1997)

PubMed id: 9405157

The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions.

J.C.Williams, A.Weijland, S.Gonfloni, A.Thompson, S.A.Courtneidge, G.Superti-Furga, R.K.Wierenga.

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.

Selected figure(s)

Figure 6.
Figure 6. Superposition of chicken and human Src. The colour code for the chicken Src residues is as in Figure 1; the human Src residues are in dark blue. Top, Superposition of the SH3 domain and the N-terminal lobe. Bottom, Superposition of the C-terminal lobe.

Figure 7.
Figure 7. Superposition of the N-terminal lobes of chicken Src and human Hck. The colour code for the chicken Src residues is as in Figure 1; the human Hck residues are in dark blue. For chicken Src side-chains of the following residues are shown: Arg95, Tyr90, Tyr136, Trp118 (SH3 domain), Leu255 (SH2-kinase linker), and Trp286, Tyr326, and Gln324 (N-ter minal domain). The equivalent residues of Hck are also shown.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 274, 757-775) copyright 1997.

Figures were selected by an automated process.