Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan AKT inhibitors

Structure

x-ray diffraction · 2 distinct chains · 35% helix, 17% strand (DSSP).

Ligands and binding sites

• SMY · (2R)-3-(1H-indol-3-yl)-1-{4-[(5S)-5-methyl-5,7-dihydrothieno[3,4-d]pyrimidin-4-yl]piperazin-1-yl}-1-oxopropan-2-amine · ligand · 2 copies · chains A, C, B, D

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

8 pockets found on a 1 Å grid, 3 with a druggability of 0.5 or more.

Interfaces

4 interfaces between chains.

• A–C · 668 Ų buried · 19 hydrogen bonds · protein-protein
• B–D · 667 Ų buried · 21 hydrogen bonds · protein-protein
• A–B · 215 Ų buried · 4 hydrogen bonds · protein-protein
• A–D · 31 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 2 modified (phosphorylation).

Compared structures

• 3OW4 · Discovery of dihydrothieno- and dihydrofuropyrimidines as potent pan Akt inhibitors · the same entry in another collection · chain A against A, TM-score 1.00
• P31749 · AlphaFold monomer V2.0 prediction for rac-alpha SERINE/THREONINE- protein kinase (P31749) · a predicted model of the same protein · chain B against A, TM-score 0.98

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P31749
• Elsewhere: RCSB PDB 3OW4 · PDBe 3OW4 · UniProt P31749