PDBsum entry 2o88

Signaling protein

PDB id: 2o88

Contents

Protein chains

58 a.a. *

11 a.a. *

Ligands

SO4 ×2

Waters ×67

* Residue conservation analysis

PDB id:

2o88

Name:

Signaling protein

Title:

Crystal structure of the n114a mutant of abl-sh3 domain complexed with a designed high-affinity peptide ligand: implications for sh3-ligand interactions

Structure:

Proto-oncogene tyrosine-protein kinase abl1. Chain: a, b. Fragment: sh3 domain, residues 64-121. Synonym: p150, c- abl, abelson murine leukemia viral oncogene homolog 1. Engineered: yes. Mutation: yes. P41 peptide. Chain: c, d.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: pbat4. Gene: abl1, abl, jtk7. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Synthetic construct.

Resolution:

1.75Å R-factor: 0.171 R-free: 0.213

Authors:

A.Camara-Artigas

Key ref:

A.Cámara-Artigas et al. (2007). Crystallization by capillary counter-diffusion and structure determination of the N114A mutant of the SH3 domain of Abl tyrosine kinase complexed with a high-affinity peptide ligand. Acta Crystallogr D Biol Crystallogr, 63, 646-652. PubMed id: 17452790 DOI: 10.1107/S0907444907011109

Date:

12-Dec-06 Release date: 01-May-07

Protein chains

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

Seq: 1130 a.a.

Struc: 58 a.a.*

Protein chains

No UniProt id for this chain

Struc: 10 a.a.

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

Enzyme reactions

• Enzyme class: Chains A, B: 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: 10.1107/S0907444907011109

Acta Crystallogr D Biol Crystallogr 63:646-652 (2007)

PubMed id: 17452790

Crystallization by capillary counter-diffusion and structure determination of the N114A mutant of the SH3 domain of Abl tyrosine kinase complexed with a high-affinity peptide ligand.

A.Cámara-Artigas, A.Palencia, J.C.Martínez, I.Luque, J.A.Gavira, J.M.García-Ruiz.

ABSTRACT

The recognition of proline-rich ligands by SH3 domains is part of the process leading to diseases such as cancer or AIDS. Understanding the molecular determinants of the binding affinity and specificity of these interactions is crucial for the development of potent inhibitors with therapeutic potential. In this study, the crystallographic structure of the N114A mutant of the SH3 domain of the Abelson leukaemia virus tyrosine kinase complexed with a high-affinity peptide is presented. The crystallization was carried out using the capillary counter-diffusion technique, which facilitates the screening, manipulation and transport of the crystals and allows the collection of X-ray data directly from the capillary in which the crystals were grown. The crystals of the N114A mutant belong to the orthorhombic P2(1)2(1)2(1) space group, with unit-cell parameters a = 48.2, b = 50.1, c = 56.4 A. The quality of the diffraction data set has allowed the structure of the complex to be determined at a resolution limit of 1.75 A.

Selected figure(s)

Figure 2.
Figure 2 Overall fold of the N114A mutant of the SH3 domain of Ab1 in complex with the p41 decapeptide. Residues in the SH3 domain-binding site are shown as green sticks. The decapeptide p41 is shown as yellow sticks. The proline residues interacting with the three hydrophobic pockets (pocket 1, Tyr70/Tyr115; pocket 2, Tyr115/Phe72/Trp99; pocket 3, Trp99/Trp110/Asn78) in the SH3 domain are indicated.

Figure 5.
Figure 5 Superposition of the N114 Abl-SH3-p41 complex (cyan) and the Abl tyrosine kinase structure (PDB code 1opk ; pale green). The SH2-kinase linker implicated in regulation of the kinase activity is coloured orange. Relevant water molecules are shown as red spheres.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 646-652) copyright 2007.

Figures were selected by an automated process.