4-(3-trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important

Structure

x-ray diffraction · 1 distinct chain · 29% helix, 24% strand (DSSP).

Ligands and binding sites

• 935 · (E)-1-(6-{4-[3-(4-methylpiperazin-1-yl)propoxy]-3-(trifluoromethyl)phenyl}pyridin-2-yl)methanimine · ligand · 2 copies · chains A, B
• 93N · 6-{4-[3-(4-methylpiperazin-1-yl)propoxy]-3-(trifluoromethyl)phenyl}pyridine-2-carbonitrile · ligand · chains A
• SO4 · Sulfate ion · ion · chains B
• GOL · Glycerol · additive · 2 copies · chains B
• PEG · Di(hydroxyethyl)ether · additive · chains A
• DMS · Dimethyl sulfoxide · additive · chains A

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

Pockets

1 pocket found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 758 Ų buried · 8 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 6 disulfide, 2 covalent (disulfide, covalent ligand).

Compared structures

• 3N3G · 4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not… · the same entry in another collection · chain A against A, TM-score 1.00
• P25774 · AlphaFold monomer V2.0 prediction for cathepsin S (P25774) · a predicted model of the same protein · chain B against A, TM-score 1.00

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 P25774
• Elsewhere: RCSB PDB 3N3G · PDBe 3N3G · UniProt P25774