› 3orn

X-ray diffraction
2.8Å resolution

Mitogen-activated protein kinase kinase 1 (MEK1) in complex with CH4987655 and MgAMP-PNP

Released:
DOI: 10.2210/pdb3orn/pdb
PDB entry 3orn coloured by chain, front view.
PDB entry 3orn coloured by chain, side view.
PDB entry 3orn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent.
Isshiki Y, Kohchi Y, Iikura H, Matsubara Y, Asoh K, Murata T, Kohchi M, Mizuguchi E, Tsujii S, Hattori K, Miura T, Yoshimura Y, Aida S, Miwa M, Saitoh R, Murao N, Okabe H, Belunis C, Janson C, Lukacs C, Schück V, Shimma N
Bioorg Med Chem Lett 21 1795-801 (2011)
PMID: 21316218

Function and Biology Details

Reaction catalysed: 
ATP + L-seryl/L-threonyl/L-tyrosyl-[protein] = ADP + O-phospho-L-seryl/O-phospho-L-threonyl/O-phospho-L-tyrosyl-[protein]
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assemblies composition:
monomeric (preferred)
homo dimer
Assembly name:
PDBe Complex ID:
PDB-CPX-169744 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dual specificity mitogen-activated protein kinase kinase 1 Chain: A
Molecule details ›
Chain: A
Length: 307 amino acids
Theoretical weight: 34.24 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q02750 (Residues: 62-393; Coverage: 76%)
Gene names: MAP2K1, MEK1, PRKMK1
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

5 bound ligands:
Ligand ANP 1 x ANP
Ligand MG 1 x MG
Ligand 3OR 1 x 3OR
Ligand PGE 1 x PGE
Ligand SO4 6 x SO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 31-ID
Spacegroup: P3121
Unit cell:
a: 136.67Å b: 136.67Å c: 60.906Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.236 0.234 0.277
Expression system: Escherichia coli

Quick links

Citations

16 review citations

MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road.
Caunt et al. (2015)
15 more

4 mentions without citation

MEK1/2 Inhibitors: Molecular Activity and Resistance Mechanisms.
Wu et al. (2015)
3 more