› 4wk7

X-ray diffraction
1.24Å resolution

Crystal structure of human ADAMTS-4 in complex with inhibitor (compound 1, 2-(4-chlorophenoxy)-N-{[(4R)-4-methyl-2,5-dioxoimidazolidin-4-yl]methyl} acetamide)

Released:
DOI: 10.2210/pdb4wk7/pdb
PDB 4wk7 coloured by chain and viewed from the front.
PDB 4wk7 coloured by chain and viewed from the side.
PDB 4wk7 coloured by chain and viewed from the top.
Source organism: Homo sapiens
Primary publication:
Identification of Potent and Selective Hydantoin Inhibitors of Aggrecanase-1 and Aggrecanase-2 Which Are Efficacious in both Chemical and Surgical Models of Osteoarthritis.
Durham TB, Klimkowski VJ, Rito CJ, Marimuthu J, Toth JL, Liu C, Durbin JD, Stout SL, Adams LA, Swearingen CA, Lin C, Chambers MG, Thirunavukkarasu K, Wiley MR
J. Med. Chem. (2014)
PMID: 25415648

Function and Biology Details

Reaction catalysed: 
Glutamyl endopeptidase. Bonds cleaved include 370-Thr-Glu-Gly-Glu-|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan.
Biochemical function:
  • not assigned
Biological process:
  • not assigned
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
A disintegrin and metalloproteinase with thrombospondin motifs 4 Chain: A
Molecule details ›
Chain: A
Length: 235 amino acids
Theoretical weight: 25.48 KDa
Source organism: Homo sapiens
Expression system: Homo sapiens
UniProt:
  • Canonical: O75173 (Residues: 213-439; Coverage: 29%)
Gene names: ADAMTS4, KIAA0688, UNQ769/PRO1563
Sequence domains: Reprolysin (M12B) family zinc metalloprotease
Structure domains: Collagenase (Catalytic Domain)

Ligands and Environments

3 bound ligands:
Ligand ZN 1 x ZN
Ligand CA 3 x CA
Ligand 3PQ 1 x 3PQ
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 31-ID
Spacegroup: P212121
Unit cell:
a: 40.506Å b: 67.923Å c: 74.581Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.196 0.196 0.213
Expression system: Homo sapiens

Quick links

Citations

1 review citation

Vitamin K-Dependent Proteins in Skeletal Development and Disease.
Stock et al. (2021)
5 other articles

6 mentions without citation

Targeting Aggrecanases for Osteoarthritis Therapy: From Zinc Chelation to Exosite Inhibition.
Cuffaro et al. (2022)
5 more