{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T09:45:14Z","timestamp":1775468714176,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Research Council of Turkey (T\u00dcB\u0130TAK)","award":["122Z429"],"award-info":[{"award-number":["122Z429"]}]},{"name":"Scientific and Technological Research Council of Turkey (T\u00dcB\u0130TAK)","award":["101061939"],"award-info":[{"award-number":["101061939"]}]},{"name":"European Union\u2019s Horizon Europe research and innovation programme under the Marie Sktodowska-Curie grant agreement","award":["122Z429"],"award-info":[{"award-number":["122Z429"]}]},{"name":"European Union\u2019s Horizon Europe research and innovation programme under the Marie Sktodowska-Curie grant agreement","award":["101061939"],"award-info":[{"award-number":["101061939"]}]},{"name":"Suna and Inan K\u0131ra\u00e7 Foundation","award":["122Z429"],"award-info":[{"award-number":["122Z429"]}]},{"name":"Suna and Inan K\u0131ra\u00e7 Foundation","award":["101061939"],"award-info":[{"award-number":["101061939"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Superoxide dismutase 1 (SOD1) is a crucial enzyme that protects cells from oxidative damage by converting superoxide radicals into H2O2 and O2. This detoxification process, essential for cellular homeostasis, relies on a precisely orchestrated catalytic mechanism involving the copper cation, while the zinc cation contributes to the structural integrity of the enzyme. This study presents the 2.3 \u00c5 crystal structure of human SOD1 (PDB ID: 9IYK), revealing an assembly of six homodimers and twelve distinct active sites. The water molecules form a complex hydrogen-bonding network that drives proton transfer and sustains active site dynamics. Our structure also uncovers subtle conformational changes that highlight the intrinsic flexibility of SOD1, which is essential for its function. Additionally, we observe how these dynamic structural features may be linked to pathological mutations associated with amyotrophic lateral sclerosis (ALS). By advancing our understanding of hSOD1\u2019s mechanistic intricacies and the influence of water coordination, this study offers valuable insights for developing therapeutic strategies targeting ALS. Our structure\u2019s unique conformations and active site interactions illuminate new facets of hSOD1 function, underscoring the critical role of structural dynamics in enzyme catalysis. Moreover, we conducted a molecular docking analysis using SOD1 for potential radical scavengers and Abelson non-receptor tyrosine kinase (c-Abl, Abl1) inhibitors targeting misfolded SOD1 aggregation along with oxidative stress and apoptosis, respectively. The results showed that CHEMBL1075867, a free radical scavenger derivative, showed the most promising docking results and interactions at the binding site of hSOD1, highlighting its promising role for further studies against SOD1-mediated ALS.<\/jats:p>","DOI":"10.3390\/ijms26094228","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"4228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9686-4943","authenticated-orcid":false,"given":"Ilkin","family":"Yapici","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3478-8258","authenticated-orcid":false,"given":"Arda Gorkem","family":"Tokur","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9711","authenticated-orcid":false,"given":"Belgin","family":"Sever","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-7669","authenticated-orcid":false,"given":"Halilibrahim","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Burdur 15030, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6977-2517","authenticated-orcid":false,"given":"Ayse Nazli","family":"Basak","sequence":"additional","affiliation":[{"name":"Suna and \u0130nan K\u0131ra\u00e7 Foundation, Neurodegeneration Research Laboratory (KUTTAM-NDAL), School of Medicine, Koc University, Istanbul 34450, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9135-5397","authenticated-orcid":false,"given":"Hasan","family":"DeMirci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, T\u00fcrkiye"},{"name":"Stanford PULSE Institute, SLAC National Laboratory, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Andr\u00e9s, C.M.C., P\u00e9rez de la Lastra, J.M., Andr\u00e9s Juan, C., Plou, F.J., and P\u00e9rez-Lebe\u00f1a, E. 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