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Adv."],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:p>\n                    Nitric oxide synthase (NOS) is a widely studied multidomain redox enzyme that produces the key signaling molecule and cytotoxic agent nitric oxide (NO) for functions that range from mammalian vasodilation to prokaryotic antibiotic resistance. NOS enzymes from metazoans and cyanobacteria rely on dynamic associations of their oxygenase and coupled diflavin reductase domains that have largely evaded detailed structural characterization. Cryo\u2013electron microscopy studies of a representative dimeric six-domain\n                    <jats:italic toggle=\"yes\">Synechococcus<\/jats:italic>\n                    NOS reveal the architecture of the full-length enzyme, which contains an unusual regulatory C2 domain, and additional nitric oxide dioxygenase (NOD) and pseudoglobin modules. Five distinct structural states depict how pterin binding couples to tight and loose oxygenase conformations and how the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -sensitive C2 domain moves over 85 angstroms to alternatively regulate either the NOS or NOD heme center. The extended carboxyl-terminal tail and its dynamic interactions highlight an added layer of regulation required by multidomain NOSs compared to other diflavin reductases.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb4529","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:58:58Z","timestamp":1771613938000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Structure and dynamics of a multidomain nitric oxide synthase regulated by a C2 domain"],"prefix":"10.1126","volume":"12","author":[{"given":"Dhruva","family":"Nair","sequence":"first","affiliation":[{"name":"Weill Institute for Cell and Molecular Biology, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8234-9991","authenticated-orcid":true,"given":"Brian R.","family":"Crane","sequence":"additional","affiliation":[{"name":"Weill Institute for Cell and Molecular Biology, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(89)80219-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-062608-103436"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr020623q"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"M. 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