PDBsum entry 4tyj

Transferase

PDB id: 4tyj

Contents

Protein chain

278 a.a.

Ligands

0LI

EDO

PO4 ×2

Waters ×56

PDB id:

4tyj

Name:

Transferase

Title:

Structural analysis of the human fibroblast growth factor receptor 4 kinase

Structure:

Fibroblast growth factor receptor 4. Chain: a. Fragment: unp residues 447-753. Synonym: fgfr-4. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgfr4, jtk2, tkf. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

2.45Å R-factor: 0.217 R-free: 0.247

Authors:

E.Lesca,A.Lammens,R.Huber,M.Augustin

Key ref:

E.Lesca et al. (2014). Structural analysis of the human fibroblast growth factor receptor 4 kinase. J Mol Biol, 426, 3744-3756. PubMed id: 25219510 DOI: 10.1016/j.jmb.2014.09.004

Date:

08-Jul-14 Release date: 24-Sep-14

Protein chain

P22455  (FGFR4_HUMAN) -  Fibroblast growth factor receptor 4 from Homo sapiens

Seq: 802 a.a.

Struc: 278 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

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

DOI no: 10.1016/j.jmb.2014.09.004

J Mol Biol 426:3744-3756 (2014)

PubMed id: 25219510

Structural analysis of the human fibroblast growth factor receptor 4 kinase.

E.Lesca, A.Lammens, R.Huber, M.Augustin.

ABSTRACT

The family of fibroblast growth factor receptors (FGFRs) plays an important and well-characterized role in a variety of pathological disorders. FGFR4 is involved in myogenesis and muscle regeneration. Mutations affecting the kinase domain of FGFR4 may cause cancer, for example, breast cancer or rhabdomyosarcoma. Whereas FGFR1-FGFR3 have been structurally characterized, the structure of the FGFR4 kinase domain has not yet been reported. In this study, we present four structures of the kinase domain of FGFR4, in its apo-form and in complex with different types of small-molecule inhibitors. The two apo-FGFR4 kinase domain structures show an activation segment similar in conformation to an autoinhibitory segment observed in the hepatocyte growth factor receptor kinase but different from the known structures of other FGFR kinases. The structures of FGFR4 in complex with the type I inhibitor Dovitinib and the type II inhibitor Ponatinib reveal the molecular interactions with different types of kinase inhibitors and may assist in the design and development of FGFR4 inhibitors.