Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 33

Structure

x-ray diffraction · 2 distinct chains · 15% helix, 46% strand (DSSP).

Ligands and binding sites

• S43 · (4~{S},5~{S},9~{S})-5-oxidanyl-4-(phenylmethyl)-9-propan-2-yl-1-oxa-3,8,11-triazacyclodocosane-2,7,10-trione · ligand · chains A, B
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 3 copies · chains A, B
• SO4 · Sulfate ion · ion · chains B
• DMS · Dimethyl sulfoxide · additive · chains B

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

Pockets

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

Interfaces

1 interface between chains.

• A–B · 3211 Ų buried · 81 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 4 disulfide, 2 glycan (disulfide, N-glycosylation).

Compared structures

• 6QBH · Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 33 · the same entry in another collection · chain A against A, TM-score 1.00
• P07339 · AlphaFold monomer V2.0 prediction for cathepsin D (P07339) · 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 P07339
• Elsewhere: RCSB PDB 6QBH · PDBe 6QBH · UniProt P07339