› 5ehy

X-ray diffraction
2.26Å resolution

Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle kinase 1 (MPS1) Using a Structure-Based Hydridization Approach

Released:
DOI: 10.2210/pdb5ehy/pdb
PDB entry 5ehy coloured by chain, front view.
PDB entry 5ehy coloured by chain, side view.
PDB entry 5ehy coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach.
Innocenti P, Woodward HL, Solanki S, Naud S, Westwood IM, Cronin N, Hayes A, Roberts J, Henley AT, Baker R, Faisal A, Mak GW, Box G, Valenti M, De Haven Brandon A, O'Fee L, Saville H, Schmitt J, Matijssen B, Burke R, van Montfort RL, Raynaud FI, Eccles SA, Linardopoulos S, Blagg J, Hoelder S
J Med Chem 59 3671-88 (2016)
PMID: 27055065

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

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-152667 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Dual specificity protein kinase TTK Chain: A
Molecule details ›
Chain: A
Length: 313 amino acids
Theoretical weight: 36.12 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P33981 (Residues: 519-808; Coverage: 34%)
Gene names: MPS1, MPS1L1, TTK
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

4 bound ligands:
Ligand 7PE 7 x 7PE
Ligand 5O4 1 x 5O4
Ligand EDO 5 x EDO
Ligand DMS 1 x DMS
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: DIAMOND BEAMLINE I04
Spacegroup: I222
Unit cell:
a: 70.616Å b: 111.453Å c: 113.694Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.186 0.185 0.207
Expression system: Escherichia coli BL21

Quick links

Citations

11 citation in other articles

Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer.
Mason et al. (2017)
10 more

1 mention without citation

Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families.
Li et al. (2022)