PDBsum entry 2fo0

Transferase

PDB id: 2fo0

Contents

Protein chain

466 a.a. *

Ligands

MYR

P16

GOL ×2

Waters ×145

* Residue conservation analysis

PDB id:

2fo0

Name:

Transferase

Title:

Organization of the sh3-sh2 unit in active and inactive forms of the c-abl tyrosine kinase

Structure:

Proto-oncogene tyrosine-protein kinase abl1 (1b isoform). Chain: a. Fragment: abl n-cap (residues 1-531, residues 15-56 deleted). Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c-abl. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.27Å R-factor: 0.210 R-free: 0.246

Authors:

B.Nagar,O.Hantschel,M.Seeliger,J.M.Davies,W.I.Weis,G.Superti-Furga, J.Kuriyan

Key ref:

B.Nagar et al. (2006). Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase. Mol Cell, 21, 787-798. PubMed id: 16543148 DOI: 10.1016/j.molcel.2006.01.035

Date:

12-Jan-06 Release date: 21-Mar-06

Protein chain

P00519  (ABL1_HUMAN) -  Tyrosine-protein kinase ABL1 from Homo sapiens

Seq: 1130 a.a.

Struc: 466 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.molcel.2006.01.035

Mol Cell 21:787-798 (2006)

PubMed id: 16543148

Organization of the SH3-SH2 unit in active and inactive forms of the c-Abl tyrosine kinase.

B.Nagar, O.Hantschel, M.Seeliger, J.M.Davies, W.I.Weis, G.Superti-Furga, J.Kuriyan.

ABSTRACT

The tyrosine kinase c-Abl is inactivated by interactions made by its SH3 and SH2 domains with the distal surface of the kinase domain. We present a crystal structure of a fragment of c-Abl which reveals that a critical N-terminal cap segment, not visualized in previous structures, buttresses the SH3-SH2 substructure in the autoinhibited state and locks it onto the distal surface of the kinase domain. Surprisingly, the N-terminal cap is phosphorylated on a serine residue that interacts with the connector between the SH3 and SH2 domains. Small-angle X-ray scattering (SAXS) analysis shows that a mutated form of c-Abl, in which the N-terminal cap and two other key contacts in the autoinhibited state are deleted, exists in an extended array of the SH3, SH2, and kinase domains. This alternative conformation of Abl is likely to prolong the active state of the kinase by preventing it from returning to the autoinhibited state.

Selected figure(s)

Figure 1.
Figure 1. Schematic Diagram of the c-Abl Constructs Used and the Structure of the Cap Region
(A) Abl^N-cap was used for both the crystal structure and SAXS analyses. Residues from the N-terminal cap in Abl^N-cap that were deleted are indicated with gray shading, and residues that were included are highlighted in pink.
(B) Surface representation of Abl^N-cap with the cap region shown as a backbone model in pink. Residues that connect the cap to the myristoyl but could not be modeled are shown as pink spheres. Helix αI of the kinase domain is colored purple. A black box indicates the region magnified in (C).
(C) Hydrophobic surface rendition of Abl^N-cap showing cap interactions with the SH2 domain and SH3-SH2 connector. Increasing hydrophobicity of the surface is indicated with darker shades of green. The cap is shown as sticks, where carbon, nitrogen, and oxygen atoms are colored orange, blue, and red, respectively. Labeled are residues that are well ordered and make direct interactions with the protein. The water molecule hydrogen bonded to Lys70 is shown as a blue sphere. Molecular figures were generated with PyMOL (DeLano, 2002).

Figure 4.
Figure 4. Shape Reconstructions
(A) Kinase domain. The backbone of the crystal structure of the c-Abl kinase domain (blue; PDB code 1OPJ) is superimposed onto the shape reconstruction (shown as green mesh).
(B) Abl^N-cap. Superimposed is the crystal structure of Abl^N-cap shown as a green backbone onto the shape reconstruction (gray mesh).
(C) Abl^activated. The kinase domain and SH2 and SH3 domains are colored red, green, and blue, respectively. Indicated on the right view is the part of the model that may correspond to the crystal structure of disassembled c-Abl from the original crystallographic analysis of c-Abl 1b. The SH3 domain was placed by visual inspection, ensuring that its C terminus was in close proximity to the N terminus of the SH2 domain.

The above figures are reprinted by permission from Cell Press: Mol Cell (2006, 21, 787-798) copyright 2006.

Figures were selected by an automated process.