4WKI: Crystal Structure Of Human Adamts-4 In Complex With Inhibitor 5- Chloro-n-{[(4s)-4-(1-methyl-1h-imidazol-2-yl)-2,5-dioxoimidazolidin- 4-yl]methyl}-1-benzofuran-2-carboxamide (compound 11)

Citation:
Abstract
A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 are zinc metalloproteases commonly referred to as aggrecanase-1 and aggrecanase-2, respectively. These enzymes are involved in the degradation of aggrecan, a key component of cartilage. Inhibitors of these enzymes could be potential osteoarthritis (OA) therapies. A series of hydantoin inhibitors of ADAMTS-4 and ADAMTS-5 were identified from a screening campaign and optimized through structure-based drug design to give hydantoin 13. Hydantoin 13 had excellent selectivity over other zinc metalloproteases such as TACE, MMP2, MMP3, MMP13, and MMP14. The compound also produced efficacy in both a chemically induced and surgical model of OA in rats.
PDB ID: 4WKIDownload
MMDB ID: 125525
PDB Deposition Date: 2014/10/2
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 1.6  Å
Source Organism:
Similar Structures:
Biological Unit for 4WKI: monomeric; determined by author and by software (PISA)
Molecular Components in 4WKI
Label Count Molecule
Protein (1 molecule)
1
a Disintegrin and Metalloproteinase With Thrombospondin Motifs 4(Gene symbol: ADAMTS4)
Molecule annotation
Chemicals (6 molecules)
1
1
2
3
3
1
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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