PDBsum entry 3eg3

Transferase

PDB id: 3eg3

Contents

Protein chain

63 a.a. *

Ligands

GOL

Waters ×36

* Residue conservation analysis

PDB id:

3eg3

Name:

Transferase

Title:

Crystal structure of the n114a mutant of abl-sh3 domain

Structure:

Proto-oncogene tyrosine-protein kinase abl1. Chain: a. Fragment: sh3 domain, residues 60-121. Synonym: p150, c- abl, abelson murine leukemia viral oncogene homolog 1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: pbat4. Gene: abl1, abl, jtk7. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.40Å R-factor: 0.210 R-free: 0.240

Authors:

A.Camara-Artigas

Key ref:

A.Palencia et al. (2010). Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl. J Biol Chem, 285, 2823-2833. PubMed id: 19906645

Date:

10-Sep-08 Release date: 15-Sep-09

Protein chain

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

Seq: 1130 a.a.

Struc: 63 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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

J Biol Chem 285:2823-2833 (2010)

PubMed id: 19906645

Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl.

A.Palencia, A.Camara-Artigas, M.T.Pisabarro, J.C.Martinez, I.Luque.

ABSTRACT

The interaction of Abl-Src homology 3 domain (SH3) with the high affinity peptide p41 is the most notable example of the inconsistency existing between the currently accepted description of SH3 complexes and their binding thermodynamic signature. We had previously hypothesized that the presence of interfacial water molecules is partially responsible for this thermodynamic behavior. We present here a thermodynamic, structural, and molecular dynamics simulation study of the interaction of p41 with Abl-SH3 and a set of mutants designed to alter the water-mediated interaction network. Our results provide a detailed description of the dynamic properties of the interfacial water molecules and a molecular interpretation of the thermodynamic effects elicited by the mutations in terms of the modulation of the water-mediated hydrogen bond network. In the light of these results, a new dual binding mechanism is proposed that provides a better description of proline-rich ligand recognition by Abl-SH3 and that has important implications for rational design.