› 1nlj

X-ray diffraction
2.4Å resolution

CRYSTAL STRUCTURE OF THE CYSTEINE PROTEASE HUMAN CATHEPSIN K IN COMPLEX WITH A COVALENT AZEPANONE INHIBITOR

Released:
DOI: 10.2210/pdb1nlj/pdb
PDB entry 1nlj coloured by chain, front view.
PDB entry 1nlj coloured by chain, side view.
PDB entry 1nlj coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Azepanone-based inhibitors of human and rat cathepsin K.
Marquis RW, Ru Y, LoCastro SM, Zeng J, Yamashita DS, Oh HJ, Erhard KF, Davis LD, Tomaszek TA, Tew D, Salyers K, Proksch J, Ward K, Smith B, Levy M, Cummings MD, Haltiwanger RC, Trescher G, Wang B, Hemling ME, Quinn CJ, Cheng HY, Lin F, Smith WW, Janson CA, Zhao B, McQueney MS, D'Alessio K, Lee CP, Marzulli A, Dodds RA, Blake S, Hwang SM, James IE, Gress CJ, Bradley BR, Lark MW, Gowen M, Veber DF
J Med Chem 44 1380-95 (2001)
PMID: 11311061

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 domain:

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 Chains: A, B
Molecule details ›
Chains: A, B
Length: 215 amino acids
Theoretical weight: 23.52 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
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

1 bound ligand:
Ligand 2CA 2 x 2CA
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: P43
Unit cell:
a: 100.96Å b: 100.96Å c: 53.694Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.263 0.263 0.295
Expression system: Spodoptera frugiperda

Quick links

Citations

12 review citations

Organic carbamates in drug design and medicinal chemistry.
Ghosh et al. (2015)
11 more

3 mentions without citation

Collagenolytic activities of the major secreted cathepsin L peptidases involved in the virulence of the helminth pathogen, Fasciola hepatica.
Robinson et al. (2011)
2 more