{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:30:21Z","timestamp":1792661421948,"version":"4.5.0"},"reference-count":53,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T00:00:00Z","timestamp":1440547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006143","name":"Department of Science and Technology, Government of Kerala","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006143","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Mutations and deletions in <jats:styled-content style=\"fixed-case\">SMARCAL<\/jats:styled-content>1, an <jats:styled-content style=\"fixed-case\">SWI<\/jats:styled-content>2\/<jats:styled-content style=\"fixed-case\">SNF<\/jats:styled-content>2 protein, cause Schimke immuno\u2010osseous dysplasia (<jats:styled-content style=\"fixed-case\">SIOD<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">SMARCAL<\/jats:styled-content>1 preferentially binds to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> molecules possessing double\u2010stranded to single\u2010stranded transition regions and mediates annealing helicase activity. The protein is critical for alleviating replication stress and maintaining genome integrity. In this study, we have analysed the <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase activity of three mutations \u2013 A468P, I548N and S579L \u2013 present in <jats:styled-content style=\"fixed-case\">SIOD<\/jats:styled-content> patients. These mutations are present in RecA\u2010like domain I of the protein. Analysis using active <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010dependent <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase A domain (<jats:styled-content style=\"fixed-case\">ADAAD<\/jats:styled-content>), an N\u2010terminal deleted construct of bovine <jats:styled-content style=\"fixed-case\">SMARCAL<\/jats:styled-content>1, showed that all three mutants were unable to hydrolyse <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>. Conformational studies indicated that the \u03b1\u2010helix and \u03b2\u2010sheet content of the mutant proteins was altered compared to the wild\u2010type protein. Molecular simulation studies confirmed that major structural changes had occurred in the mutant proteins. These changes included alteration of a loop region connecting motif Ia and <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>. As motif Ia has been implicated in <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> binding, ligand binding studies were done using fluorescence spectroscopy. These studies revealed that the <jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub> for protein\u2013<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> interaction in the presence of <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> was indeed altered in the case of mutant proteins compared to the wild\u2010type. Finally, <jats:italic>in\u00a0vivo<\/jats:italic> studies were done to complement the <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0silico<\/jats:italic> studies. The results from these experiments demonstrate that mutations in human <jats:styled-content style=\"fixed-case\">SMARCAL<\/jats:styled-content>1 that result in loss in <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase activity lead to increased replication stress and therefore possibly manifestation of <jats:styled-content style=\"fixed-case\">SIOD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/febs.13382","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T04:17:08Z","timestamp":1437452228000},"page":"3841-3859","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Ligand\u2010induced conformation changes drive <scp>ATP<\/scp> hydrolysis and function in <scp>SMARCAL<\/scp>1"],"prefix":"10.1111","volume":"282","author":[{"given":"Meghna","family":"Gupta","sequence":"first","affiliation":[{"name":"School of Life Sciences Jawaharlal Nehru University New Delhi 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