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A. Van Dormael Fund for radio-pharmaco-chemical applications in neurodegenerative diseases"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr D Struct Biol","Acta Crystallogr D","Acta Cryst D","Acta Cryst D Struct Biol","Acta Cryst Sect D","Acta Cryst Sect D Struct Biol","Acta Crystallogr Sect D","Acta Crystallogr Sect D Struct Biol","Acta Crystallogr D Biol Crystallogr","Acta Cryst D Biol Cryst"],"accepted":{"date-parts":[[2026,2,18]]},"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>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\u2005\u00c5 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.<\/jats:p>","DOI":"10.1107\/s2059798326001749","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:47:08Z","timestamp":1773049628000},"page":"330-335","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":0,"title":["The human TIMP-1 unbound structure provides a platform for fragment screening"],"prefix":"10.1107","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3599-846X","authenticated-orcid":true,"given":"Ahmed","family":"Shemy","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"department":["Biomolecular Modelling and Design Lab, Department of Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-1763","authenticated-orcid":true,"given":"Jana","family":"Van Broeckhoven","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04nbhqj75","id-type":"ROR","asserted-by":"publisher"}],"department":["Neuro-Immune Connections and Repair (NIC&R) Lab, Department of Immunology and Infection, Biomedical Research Institute"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-406X","authenticated-orcid":true,"given":"Niels","family":"Hellings","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04nbhqj75","id-type":"ROR","asserted-by":"publisher"}],"department":["Neuro-Immune Connections and Repair (NIC&R) Lab, Department of Immunology and Infection, Biomedical Research Institute"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnout","family":"Voet","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f950310","id-type":"ROR","asserted-by":"publisher"}],"department":["Biomolecular Modelling and Design Lab, Department of Chemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"chr5010_bb1","doi-asserted-by":"crossref","first-page":"7950","DOI":"10.1021\/bi034545s","volume":"42","author":"Arumugam","year":"2003","journal-title":"Biochemistry"},{"key":"chr5010_bb3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"Chen","year":"2010","journal-title":"Acta Cryst. 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