PDBsum entry 3gql

Transferase/transferase inhibitor

PDB id: 3gql

Contents

Protein chain

287 a.a. *

Ligands

GQL ×3

Waters ×187

* Residue conservation analysis

PDB id:

3gql

Name:

Transferase/transferase inhibitor

Title:

Crystal structure of activated receptor tyrosine kinase in complex with substrates

Structure:

Basic fibroblast growth factor receptor 1. Chain: a, b, c. Fragment: protein kinase domain. Synonym: fgfr-1, bfgf-r, fms-like tyrosine kinase 2, c-fgr. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgfbr, fgfr1, flg, flt2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.80Å R-factor: 0.252 R-free: 0.289

Authors:

J.H.Bae,E.D.Lew,S.Yuzawa,F.Tome,I.Lax,J.Schlessinger

Key ref:

J.H.Bae et al. (2009). The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site. Cell, 138, 514-524. PubMed id: 19665973

Date:

24-Mar-09 Release date: 18-Aug-09

Protein chains

P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1 from Homo sapiens

Seq: 822 a.a.

Struc: 287 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.2.7.10.1 - receptor 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

Cell 138:514-524 (2009)

PubMed id: 19665973

The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site.

J.H.Bae, E.D.Lew, S.Yuzawa, F.Tomé, I.Lax, J.Schlessinger.

ABSTRACT

SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. However, the modest binding affinity of SH2 domains to pY containing peptides may not account for and likely represents an oversimplified mechanism for regulation of selectivity of signaling pathways in living cells. Here we describe the crystal structure of the activated tyrosine kinase domain of FGFR1 in complex with a phospholipase Cgamma fragment. The structural and biochemical data and experiments with cultured cells show that the selectivity of phospholipase Cgamma binding and signaling via activated FGFR1 are determined by interactions between a secondary binding site on an SH2 domain and a region in FGFR1 kinase domain in a phosphorylation independent manner. These experiments reveal a mechanism for how SH2 domain selectivity is regulated in vivo to mediate a specific cellular process.