PDBsum entry 1y57

Transferase

PDB id: 1y57

Contents

Protein chain

452 a.a. *

Ligands

SO4 ×5

MPZ

Waters ×315

* Residue conservation analysis

PDB id:

1y57

Name:

Transferase

Title:

Structure of unphosphorylated c-src in complex with an inhibitor

Structure:

Proto-oncogene tyrosine-protein kinase src. Chain: a. Fragment: sh3 sh2 and kinase domains. Synonym: p60-src, c-src. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: src. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

1.91Å R-factor: 0.189 R-free: 0.213

Authors:

S.W.Cowan-Jacob,G.Fendrich,P.W.Manley,W.Jahnke,D.Fabbro,J.Liebetanz, T.Meyer

Key ref:

S.W.Cowan-Jacob et al. (2005). The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation. Structure, 13, 861-871. PubMed id: 15939018 DOI: 10.1016/j.str.2005.03.012

Date:

02-Dec-04 Release date: 21-Jun-05

Protein chain

P12931  (SRC_HUMAN) -  Proto-oncogene tyrosine-protein kinase Src from Homo sapiens

Seq: 536 a.a.

Struc: 452 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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: 10.1016/j.str.2005.03.012

Structure 13:861-871 (2005)

PubMed id: 15939018

The crystal structure of a c-Src complex in an active conformation suggests possible steps in c-Src activation.

S.W.Cowan-Jacob, G.Fendrich, P.W.Manley, W.Jahnke, D.Fabbro, J.Liebetanz, T.Meyer.

ABSTRACT

The regulation of the activity of Abl and Src family tyrosine kinases is mediated by intramolecular interactions between the SH3, SH2, and kinase (SH1) domains. We have determined the crystal structure of an unphosphorylated form of c-Src in which the SH2 domain is not bound to the C-terminal tail. This results in an open structure where the kinase domain adopts an active conformation and the C terminus binds within a hydrophobic pocket in the C-terminal lobe. NMR binding studies support the hypothesis that an N-terminal myristate could bind in this pocket, as observed for Abl, suggesting that c-Src may also be regulated by myristate binding. In addition, the structure contains a des-methyl analog of the antileukemia drug imatinib (STI571; Gleevec). This structure reveals why the drug shows a low affinity for active kinase conformations, contributing to its excellent kinase selectivity profile.

Selected figure(s)

Figure 2.
Figure 2. Conformational States of c-Src
Comparison of the structures of human c-Src phosphorylated on Tyr527 (left) and in the unphosphorylated state (right). Both structures have the same orientation with respect to their C-terminal lobes, which were superimposed. The ribbon diagrams are colored from dark blue at the N terminus to red at the C terminus; thus, the SH3 domain is blue, the SH2 domain is light blue and green, the linker is aqua, the N-terminal lobe is green, the C-terminal lobe is light green and orange, the activation loop is yellow, and the C-terminal tail is red. The ligands (magenta), sulfate groups (yellow and red), and certain side chains (yellow) discussed in the text are also represented.

The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 861-871) copyright 2005.

Figure was selected by an automated process.