› 4wke

X-ray diffraction
1.62Å resolution

Crystal structure of human ADAMTS-4 in complex with inhibitor 5-chloro-N-{[(4R)-2,5-dioxo-4-(1,3-thiazol-2-yl)imidazolidin-4-yl]methyl}-1-benzofuran-2-carboxamide (compound 10)

Released:
DOI: 10.2210/pdb4wke/pdb
PDB entry 4wke coloured by chain, front view.
PDB entry 4wke coloured by chain, side view.
PDB entry 4wke coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that 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 L, Swearingen C, Lin C, Chambers MG, Thirunavukkarasu K, Wiley MR
J Med Chem 57 10476-85 (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:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-130878 (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

4 bound ligands:
Ligand ZN 1 x ZN
Ligand CA 3 x CA
Ligand EDO 3 x EDO
Ligand 3PU 1 x 3PU
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 31-ID
Spacegroup: P212121
Unit cell:
a: 40.275Å b: 68.035Å c: 74.765Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.188 0.187 0.209
Expression system: Homo sapiens

Quick links

Citations

1 review citation

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

2 mentions without citation

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