9RWM
Crystal structure of human ADAMTS-5 Cb and Spacer domains
Summary for 9RWM
| Entry DOI | 10.2210/pdb9rwm/pdb |
| Descriptor | A disintegrin and metalloproteinase with thrombospondin motifs 5 (2 entities in total) |
| Functional Keywords | spacer domain, jelly-roll, cys rich domain, protein binding |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 3 |
| Total formula weight | 64447.63 |
| Authors | |
| Primary citation | Milani, M.,Visintin, M.,Krastanova, I.,Visentini, M.,Margotti, E.,Ugolini, G.,Bolognesi, M.,Rovati, L.C.,Mastrangelo, E. Structure, substrate recognition and therapeutic targeting of the human ADAMTS-5 spacer domain. Acta Crystallogr D Struct Biol, 82:53-61, 2026 Cited by PubMed Abstract: The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 motifs) family of secreted metalloproteinases plays essential roles in extracellular matrix remodeling. ADAMTS-5 contributes to cartilage degradation, cleaving proteoglycans such as aggrecan and versican, and being involved in both physiological tissue turnover and pathological processes such as osteoarthritis and atherosclerosis. Although structural insights into its catalytic domain have informed inhibitor development, the role of ancillary domains, particularly the spacer domain, in substrate recognition and specificity remains underexplored. Here, we report the crystal structure of a segment of human ADAMTS-5 encompassing the C-terminal portion of the cysteine-rich domain and the spacer domain (residues 694-876). This structure reveals critical features of the spacer domain, including the hypervariable loops that function as exosites essential for the binding of aggrecan and versican. Our findings provide new structural insights into the molecular determinants of the substrate specificity of ADAMTS-5 and underscore the spacer domain as a promising target for the development of selective inhibitors. PubMed: 41334750DOI: 10.1107/S2059798325010290 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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