Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 9

Structure

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

Ligands and binding sites

• HWE · (3~{S},7~{S},8~{S})-7-oxidanyl-8-(phenylmethyl)-3-propan-2-yl-1,4,9-triazacyclohenicosane-2,5,10-trione · ligand · chains A, B
• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 4 copies · chains A, B
• BMA · beta-D-mannopyranose · sugar
• SO4 · Sulfate ion · ion · 2 copies · chains B
• PO3 · Phosphite ion · ion · chains A, B
• DMS · Dimethyl sulfoxide · additive · chains A, 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 · 3213 Ų buried · 82 hydrogen bonds · protein-protein

Modifications

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

Compared structures

• 6QCB · Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 9 · 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 6QCB · PDBe 6QCB · UniProt P07339