› 4x6j

X-ray diffraction
1.59Å resolution

Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors.

Released:
DOI: 10.2210/pdb4x6j/pdb
PDB entry 4x6j coloured by chain, front view.
PDB entry 4x6j coloured by chain, side view.
PDB entry 4x6j coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Development of N-(Functionalized benzoyl)-homocycloleucyl-glycinonitriles as Potent Cathepsin K Inhibitors.
Borišek J, Vizovišek M, Sosnowski P, Turk B, Turk D, Mohar B, Novič M
J Med Chem 58 6928-37 (2015)
PMID: 26280490

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:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-154996 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Cathepsin K Chain: A
Molecule details ›
Chain: A
Length: 215 amino acids
Theoretical weight: 23.52 KDa
Source organism: Homo sapiens
Expression system: Komagataella phaffii GS115
UniProt:
  • Canonical: P43235 (Residues: 115-329; Coverage: 69%)
Gene names: CTSK, CTSO, CTSO2
Sequence domains: Papain family cysteine protease
Structure domains: Cysteine proteinases

Ligands and Environments

5 bound ligands:
Ligand GOL 1 x GOL
Ligand CL 1 x CL
Ligand K 1 x K
Ligand PGO 3 x PGO
Ligand 3Y2 1 x 3Y2
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: BRUKER AXS MICROSTAR
Spacegroup: P21
Unit cell:
a: 47.219Å b: 44.403Å c: 51.354Å
α: 90° β: 116.42° γ: 90°
R-values:
R R work R free
0.186 0.183 0.238
Expression system: Komagataella phaffii GS115

Quick links

Citations

2 review citations

Advances in the discovery of cathepsin K inhibitors on bone resorption.
Lu et al. (2018)
1 more