9SOS
Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1)
Summary for 9SOS
| Entry DOI | 10.2210/pdb9sos/pdb |
| Descriptor | Metalloproteinase inhibitor 1 (2 entities in total) |
| Functional Keywords | hydrolase inhibitor, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 20732.85 |
| Authors | |
| Primary citation | Shemy, A.,Van Broeckhoven, J.,Hellings, N.,Voet, A. The human TIMP-1 unbound structure provides a platform for fragment screening. Acta Crystallogr D Struct Biol, 82:330-335, 2026 Cited by PubMed Abstract: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a critical regulator of extracellular matrix remodelling and an important mediator of remyelination in demyelinating disorders such as multiple sclerosis. In addition, TIMP-1 has emerged as a promising therapeutic target in cancer due to its interaction with CD63, which promotes tumorigenic signalling and carcinogenesis. Although several structures of TIMP-1 bound to matrix metalloproteinases have been reported, no unbound structure with all druggable sites available has previously been reported. Here, we present the first unbound crystal structure of human TIMP-1, resolved at 1.95 Å resolution. Comparison with the MMP-bound complex reveals localized conformational changes and altered intramolecular hydrogen bonding in the unbound structure, indicating increased structural plasticity in the absence of the protease. Crystals were obtained in multiple conditions, but only two diffracted to high resolution. Although optimization and seeding did not significantly improve the morphology, the additive screen enhanced both the morphology and reproducibility and provided intrinsic cryoprotection. The resulting crystal form proved compatible with soaking-based screening campaigns, providing a robust structural basis for the discovery of TIMP-1 ligands with clinical potential. PubMed: 41834537DOI: 10.1107/S2059798326001749 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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