PDBsum entry 4tzi

Transferase

PDB id: 4tzi

Contents

Protein chains

110 a.a.

Waters ×105

PDB id:

4tzi

Name:

Transferase

Title:

Structure of unliganded lyn sh2 domain

Structure:

Tyrosine-protein kinase lyn. Chain: a, b. Fragment: sh2 domain residues 115-229. Synonym: v-yes-1 yamaguchi sarcoma viral related oncogene homolog, p53lyn,p56lyn. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: lyn. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.203 R-free: 0.254

Authors:

L.E.Wybenga-Groot

Key ref:

L.L.Jin et al. (2015). Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its binding affinity and specificity. Mol Cell Proteomics, 14, 695-706. PubMed id: 25587033 DOI: 10.1074/mcp.M114.044404

Date:

10-Jul-14 Release date: 21-Jan-15

Protein chains

P25911  (LYN_MOUSE) -  Tyrosine-protein kinase Lyn from Mus musculus

Seq: 512 a.a.

Struc: 110 a.a.

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: 10.1074/mcp.M114.044404

Mol Cell Proteomics 14:695-706 (2015)

PubMed id: 25587033

Tyrosine phosphorylation of the Lyn Src homology 2 (SH2) domain modulates its binding affinity and specificity.

L.L.Jin, L.E.Wybenga-Groot, J.Tong, P.Taylor, M.D.Minden, S.Trudel, C.J.McGlade, M.F.Moran.

ABSTRACT

Src homology 2 (SH2) domains are modular protein structures that bind phosphotyrosine (pY)-containing polypeptides and regulate cellular functions through protein-protein interactions. Proteomics analysis showed that the SH2 domains of Src family kinases are themselves tyrosine phosphorylated in blood system cancers, including acute myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. Using the Src family kinase Lyn SH2 domain as a model, we found that phosphorylation at the conserved SH2 domain residue Y(194) impacts the affinity and specificity of SH2 domain binding to pY-containing peptides and proteins. Analysis of the Lyn SH2 domain crystal structure supports a model wherein phosphorylation of Y(194) on the EF loop modulates the binding pocket that engages amino acid side chains at the pY+2/+3 position. These data indicate another level of regulation wherein SH2-mediated protein-protein interactions are modulated by SH2 kinases and phosphatases.