› 7qbo

X-ray diffraction
1.9Å resolution

Structure of the activation intermediate of cathepsin K in complex with the azadipeptide nitrile inhibitor Gu1303

Released:
DOI: 10.2210/pdb7qbo/pdb
PDB entry 7qbo coloured by chain, front view.
PDB entry 7qbo coloured by chain, side view.
PDB entry 7qbo coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Highly potent inhibitors of cathepsin K with a differently positioned cyanohydrazide warhead: structural analysis of binding mode to mature and zymogen-like enzymes.
Benýšek J, Buša M, Rubešová P, Fanfrlík J, Lepšík M, Brynda J, Matoušková Z, Bartz U, Horn M, Gütschow M, Mareš M
J Enzyme Inhib Med Chem 37 515-526 (2022)
PMID: 35144520

Function and Biology Details

Reaction catalysed: 
Broad proteolytic activity. With small-molecule substrates and inhibitors, the major determinant of specificity is P2, which is preferably Leu, Met > Phe, and not Arg.
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
hetero dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-154997 (preferred)
Entry contents:
2 distinct polypeptide molecules
Macromolecules (2 distinct):
Cathepsin K Chain: A
Molecule details ›
Chain: A
Length: 216 amino acids
Theoretical weight: 23.68 KDa
Source organism: Homo sapiens
Expression system: Komagataella phaffii GS115
UniProt:
  • Canonical: P43235 (Residues: 114-329; Coverage: 69%)
Gene names: CTSK, CTSO, CTSO2
Sequence domains: Papain family cysteine protease
Cathepsin K Chain: P
Molecule details ›
Chain: P
Length: 74 amino acids
Theoretical weight: 8.98 KDa
Source organism: Homo sapiens
Expression system: Komagataella phaffii GS115
UniProt:
  • Canonical: P43235 (Residues: 16-89; Coverage: 24%)
Gene names: CTSK, CTSO, CTSO2
Sequence domains: Cathepsin propeptide inhibitor domain (I29)

Ligands and Environments

4 bound ligands:
Ligand 9ZG 1 x 9ZG
Ligand EDO 3 x EDO
Ligand CL 1 x CL
Ligand MG 1 x MG
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: BESSY BEAMLINE 14.1
Spacegroup: P43212
Unit cell:
a: 103.214Å b: 103.214Å c: 54.985Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.167 0.164 0.212
Expression system: Komagataella phaffii GS115

Quick links

Citations

3 review citations

Cathepsin K: A Versatile Potential Biomarker and Therapeutic Target for Various Cancers.
Qian et al. (2022)
2 more

1 mention without citation

Highly potent inhibitors of cathepsin K with a differently positioned cyanohydrazide warhead: structural analysis of binding mode to mature and zymogen-like enzymes.
Benýšek et al. (2022)