› 4r1v

X-ray diffraction
1.2Å resolution

Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors

Released:
DOI: 10.2210/pdb4r1v/pdb
PDB entry 4r1v coloured by chain, front view.
PDB entry 4r1v coloured by chain, side view.
PDB entry 4r1v coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors.
Dorsch D, Schadt O, Stieber F, Meyring M, Grädler U, Bladt F, Friese-Hamim M, Knühl C, Pehl U, Blaukat A
Bioorg Med Chem Lett 25 1597-602 (2015)
PMID: 25736998

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-140186 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Hepatocyte growth factor receptor Chain: A
Molecule details ›
Chain: A
Length: 291 amino acids
Theoretical weight: 32.99 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P08581 (Residues: 1055-1345; Coverage: 21%)
Gene name: MET
Sequence domains: Protein tyrosine and serine/threonine kinase
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand 3E8 1 x 3E8
Ligand GBL 3 x GBL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06DA
Spacegroup: P21
Unit cell:
a: 38Å b: 43.038Å c: 84.844Å
α: 90° β: 92.23° γ: 90°
R-values:
R R work R free
0.146 0.146 0.176
Expression system: Spodoptera frugiperda

Quick links

Citations

7 review citations

The therapeutic journey of pyridazinone.
Akhtar et al. (2016)
6 more

12 mentions without citation

An overview of kinase downregulators and recent advances in discovery approaches.
Wang et al. (2021)
11 more