PDBsum entry 6lvm

Transferase

PDB id: 6lvm

Contents

Protein chain

288 a.a.

Ligands

EVR

Waters ×31

PDB id:

6lvm

Name:

Transferase

Title:

Crystal structure of fgfr3 in complex with pyrimidine derivative

Structure:

Fibroblast growth factor receptor 3. Chain: a. Synonym: fgfr-3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fgfr3, jtk4. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.53Å R-factor: 0.211 R-free: 0.279

Authors:

Y.Echizen,Y.Tateishi,Y.Amano

Key ref:

I.Kuriwaki et al. (2020). Structure-based drug design of 1,3,5-triazine and pyrimidine derivatives as novel FGFR3 inhibitors with high selectivity over VEGFR2. Bioorg Med Chem, 28, 115453. PubMed id: 32278710 DOI: 10.1016/j.bmc.2020.115453

Date:

04-Feb-20 Release date: 08-Apr-20

Protein chain

P22607  (FGFR3_HUMAN) -  Fibroblast growth factor receptor 3 from Homo sapiens

Seq: 806 a.a.

Struc: 288 a.a.*

* PDB and UniProt seqs differ at 5 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.bmc.2020.115453

Bioorg Med Chem 28:115453 (2020)

PubMed id: 32278710

Structure-based drug design of 1,3,5-triazine and pyrimidine derivatives as novel FGFR3 inhibitors with high selectivity over VEGFR2.

I.Kuriwaki, M.Kameda, H.Hisamichi, S.Kikuchi, K.Iikubo, Y.Kawamoto, H.Moritomo, Y.Kondoh, Y.Amano, Y.Tateishi, Y.Echizen, Y.Iwai, A.Noda, H.Tomiyama, T.Suzuki, M.Hirano.

ABSTRACT

Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer. We identified 1,3,5-triazine derivative 18b and pyrimidine derivative 40a as novel structures with potent and highly selective FGFR3 inhibitory activity over vascular endothelial growth factor receptor 2 (VEGFR2) using a structure-based drug design (SBDD) approach. X-ray crystal structure analysis suggests that interactions between 18b and amino acid residues located in the solvent region (Lys476 and Met488), and between 40a and Met529 located in the back pocket of FGFR3 may underlie the potent FGFR3 inhibitory activity and high kinase selectivity over VEGFR2.