{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:59:20Z","timestamp":1768726760324,"version":"3.49.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology","award":["DST-FIST: SR\/FST\/LS-I\/2017(C)"],"award-info":[{"award-number":["DST-FIST: SR\/FST\/LS-I\/2017(C)"]}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["ISRM\/12(04)\/2019"],"award-info":[{"award-number":["ISRM\/12(04)\/2019"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["09\/490(0103)\/2019"],"award-info":[{"award-number":["09\/490(0103)\/2019"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["Ref. No. 17\/06\/2018(i) EU-V"],"award-info":[{"award-number":["Ref. No. 17\/06\/2018(i) EU-V"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012117","name":"Lady Tata Memorial Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012117","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal human motor neuron disease leading to muscle atrophy and paralysis. Mutations in superoxide dismutase 1 (SOD1) are associated with familial ALS (fALS). The SOD1 mutants in ALS have a toxic-gain of function by destabilizing the functional SOD1 homodimer, consequently inducing fibril-like aggregation with a cytotoxic non-native trimer intermediate. Therefore, reducing SOD1 oligomerization <jats:italic>via<\/jats:italic> chemical modulators is an optimal therapy in ALS. Here, we report the discovery of Phialomustin-B, an unsaturated secondary metabolite from the endophytic fungus <jats:italic>Phialophora mustea<\/jats:italic>, as a modulator of SOD1 aggregation. The crystal structure of the SOD1-Phialomustin complex refined to 1.90 \u00c5 resolution demonstrated for the first time that the ligand binds to the dimer interface and the lateral region near the electrostatic loop. The aggregation analyses of SOD1<jats:sup>WT<\/jats:sup> and the disease mutant SOD1<jats:sup>A4V<\/jats:sup> revealed that Phialomustin-B reduces cytotoxic trimerization. We propose that Phialomustin-B is a potent lead molecule with therapeutic potential in fALS.<\/jats:p>","DOI":"10.1371\/journal.pone.0298196","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T18:28:37Z","timestamp":1709749717000},"page":"e0298196","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9905-9464","authenticated-orcid":true,"given":"Sruthi","family":"Unni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padmini","family":"Kommu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snehal","family":"Aouti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yedukondalu","family":"Nalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. M. Srinivas","family":"Bharath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asif","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8434-828X","authenticated-orcid":true,"given":"Balasundaram","family":"Padmanabhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"pone.0298196.ref001","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrneurol.2011.153","article-title":"Clinical diagnosis and management of amyotrophic lateral sclerosis","volume":"7","author":"O. Hardiman","year":"2011","journal-title":"Nat. Rev. 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Madhuranthakam","year":"2021","journal-title":"ACS Omega, American Chemical Society"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298196","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T18:29:13Z","timestamp":1709749753000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0298196"}},"subtitle":[],"editor":[{"given":"Rajiv Kumar","family":"Kar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,6]]},"references-count":58,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0298196","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,6]]}}}