The alkyne moiety as a latent electrophile in irreversible covalent small molecule inhibitors of cathepsin K

Structure

x-ray diffraction · 1 distinct chain · 29% helix, 22% strand (DSSP).

Ligands and binding sites

• HVW · (2~{S})-4-methyl-~{N}-prop-2-enyl-2-[[(1~{S})-2,2,2-tris(fluoranyl)-1-[4-(4-methylsulfonylphenyl) phenyl]ethyl]amino]pentanamide · ligand · 2 copies · chains A, B
• CA · Calcium ion · metal · chains A, B
• CL · Chloride ion · ion · 2 copies · chains A, B

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

Pockets

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

Interfaces

1 interface between chains.

• A–B · 421 Ų buried · 19 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 5 disulfide, 2 covalent (disulfide, covalent ligand).

Compared structures

• 6QBS · The Alkyne Moiety as a Latent Electrophile in Irreversible Covalent Small Molecule… · the same entry in another collection · chain A against A, TM-score 1.00
• P43235 · AlphaFold monomer V2.0 prediction for cathepsin K (P43235) · a predicted model of the same protein · chain A 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 P43235
• Elsewhere: RCSB PDB 6QBS · PDBe 6QBS · UniProt P43235