› 4zlo

X-ray diffraction
2.5Å resolution

Serine/threonine-protein kinase PAK1 complexed with a dibenzodiazepine: identification of an allosteric site on PAK1

Released:
DOI: 10.2210/pdb4zlo/pdb
PDB entry 4zlo coloured by chain, front view.
PDB entry 4zlo coloured by chain, side view.
PDB entry 4zlo coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor.
Karpov AS, Amiri P, Bellamacina C, Bellance MH, Breitenstein W, Daniel D, Denay R, Fabbro D, Fernandez C, Galuba I, Guerro-Lagasse S, Gutmann S, Hinh L, Jahnke W, Klopp J, Lai A, Lindvall MK, Ma S, Möbitz H, Pecchi S, Rummel G, Shoemaker K, Trappe J, Voliva C, Cowan-Jacob SW, Marzinzik AL
ACS Med Chem Lett 6 776-81 (2015)
PMID: 26191365

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-171570 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine/threonine-protein kinase PAK 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 297 amino acids
Theoretical weight: 33.34 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q13153 (Residues: 249-545; Coverage: 55%)
Gene name: PAK1
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

2 bound ligands:
Ligand 4PV 1 x 4PV
Ligand GOL 1 x GOL
1 modified residue:
Ligand TPO 2 x TPO

Experiments and Validation Details

Entry percentile scores
X-ray source: RIGAKU FR-E SUPERBRIGHT
Spacegroup: P21
Unit cell:
a: 63.514Å b: 79.34Å c: 65.789Å
α: 90° β: 108.11° γ: 90°
R-values:
R R work R free
0.196 0.195 0.222
Expression system: Escherichia coli

Quick links

Citations

11 review citations

Trends in kinase drug discovery: targets, indications and inhibitor design.
Attwood et al. (2021)
10 more

5 mentions without citation

Assessing Lysine and Cysteine Reactivities for Designing Targeted Covalent Kinase Inhibitors.
Liu et al. (2019)
4 more