› 4ejn

X-ray diffraction
2.19Å resolution

Crystal structure of autoinhibited form of AKT1 in complex with N-(4-(5-(3-acetamidophenyl)-2-(2-aminopyridin-3-yl)-3H-imidazo[4,5-b]pyridin-3-yl)benzyl)-3-fluorobenzamide

Released:
DOI: 10.2210/pdb4ejn/pdb
PDB entry 4ejn coloured by chain, front view.
PDB entry 4ejn coloured by chain, side view.
PDB entry 4ejn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent Akt inhibitors.
Ashwell MA, Lapierre JM, Brassard C, Bresciano K, Bull C, Cornell-Kennon S, Eathiraj S, France DS, Hall T, Hill J, Kelleher E, Khanapurkar S, Kizer D, Koerner S, Link J, Liu Y, Makhija S, Moussa M, Namdev N, Nguyen K, Nicewonger R, Palma R, Szwaya J, Tandon M, Uppalapati U, Vensel D, Volak LP, Volckova E, Westlund N, Wu H, Yang RY, Chan TC
J Med Chem 55 5291-310 (2012)
PMID: 22533986

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-152081 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
RAC-alpha serine/threonine-protein kinase Chain: A
Molecule details ›
Chain: A
Length: 446 amino acids
Theoretical weight: 51.75 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P31749 (Residues: 2-446; Coverage: 93%)
Gene names: AKT1, PKB, RAC
Sequence domains:
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand 0R4 1 x 0R4
Ligand SBT 1 x SBT
Ligand EDO 1 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: NSLS BEAMLINE X29A
Spacegroup: P212121
Unit cell:
a: 44.508Å b: 88.214Å c: 126.936Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.239 0.237 0.276
Expression system: Spodoptera frugiperda

Quick links

Citations

8 review citations

Akt inhibitors in cancer treatment: The long journey from drug discovery to clinical use (Review).
Nitulescu et al. (2016)
7 more

43 mentions without citation

Computer-Aided Identification of Kinase-Targeted Small Molecules for Cancer: A Review on AKT Protein.
Primavera et al. (2023)
42 more