PDBsum entry 4omo

Transferase

PDB id: 4omo

Contents

Protein chains

61 a.a.

59 a.a.

Ligands

EPE

Metals

_NI ×2

Waters ×155

PDB id:

4omo

Name:

Transferase

Title:

Crystal structure of thE C-src tyrosine kinase sh3 domain mutant q128e

Structure:

Proto-oncogene tyrosine-protein kinase src. Chain: a, b. Fragment: sh3 domain. Synonym: proto-oncogenE C-src, pp60c-src, p60-src. Engineered: yes. Mutation: yes

Source:

Gallus gallus. Bantam,chickens. Organism_taxid: 9031. Gene: src. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.04Å R-factor: 0.149 R-free: 0.168

Authors:

A.Camara-Artigas,J.Bacarizo

Key ref:

J.Bacarizo et al. (2014). Electrostatic effects in the folding of the SH3 domain of the c-Src tyrosine kinase: pH-dependence in 3D-domain swapping and amyloid formation. Plos One, 9, e113224. PubMed id: 25490095 DOI: 10.1371/journal.pone.0113224

Date:

27-Jan-14 Release date: 10-Dec-14

Protein chain

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

Seq: 533 a.a.

Struc: 61 a.a.*

Protein chain

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

Seq: 533 a.a.

Struc: 59 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

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: 10.1371/journal.pone.0113224

Plos One 9:e113224 (2014)

PubMed id: 25490095

Electrostatic effects in the folding of the SH3 domain of the c-Src tyrosine kinase: pH-dependence in 3D-domain swapping and amyloid formation.

J.Bacarizo, S.Martinez-Rodriguez, J.M.Martin-Garcia, M.Andujar-Sanchez, E.Ortiz-Salmeron, J.L.Neira, A.Camara-Artigas.

ABSTRACT

The SH3 domain of the c-Src tyrosine kinase (c-Src-SH3) aggregates to form intertwined dimers and amyloid fibrils at mild acid pHs. In this work, we show that a single mutation of residue Gln128 of this SH3 domain has a significant effect on: (i) its thermal stability; and (ii) its propensity to form amyloid fibrils. The Gln128Glu mutant forms amyloid fibrils at neutral pH but not at mild acid pH, while Gln128Lys and Gln128Arg mutants do not form these aggregates under any of the conditions assayed. We have also solved the crystallographic structures of the wild-type (WT) and Gln128Glu, Gln128Lys and Gln128Arg mutants from crystals obtained at different pHs. At pH 5.0, crystals belong to the hexagonal space group P6522 and the asymmetric unit is formed by one chain of the protomer of the c-Src-SH3 domain in an open conformation. At pH 7.0, crystals belong to the orthorhombic space group P212121, with two molecules at the asymmetric unit showing the characteristic fold of the SH3 domain. Analysis of these crystallographic structures shows that the residue at position 128 is connected to Glu106 at the diverging β-turn through a cluster of water molecules. Changes in this hydrogen-bond network lead to the displacement of the c-Src-SH3 distal loop, resulting also in conformational changes of Leu100 that might be related to the binding of proline rich motifs. Our findings show that electrostatic interactions and solvation of residues close to the folding nucleation site of the c-Src-SH3 domain might play an important role during the folding reaction and the amyloid fibril formation.