{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:40:28Z","timestamp":1790872828080,"version":"4.1.0"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,11,25]]},"abstract":"<jats:p>\n                    Overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of many diseases. iNOS is active only as a homodimer. Dimerization of iNOS represents a potentially critical target for therapeutic intervention. In this study, we show that intracellular iNOS forms dimers that are \u201dundisruptable\u201d by boiling, denaturants, or reducing agents. Undisruptable (UD) dimers are clearly distinguishable from the easily dissociated dimers formed by iNOS\n                    <jats:italic>in vitro<\/jats:italic>\n                    . UD dimers do not form in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    -expressed iNOS and could not be assembled\n                    <jats:italic>in vitro<\/jats:italic>\n                    , which suggests that an\n                    <jats:italic>in vivo<\/jats:italic>\n                    cellular process is required for their formation. iNOS UD dimers are not affected by intracellular depletion of H\n                    <jats:sub>4<\/jats:sub>\n                    B. However, the mutation of Cys-115 (critical for zinc binding) greatly affects the formation of UD dimers. This study reveals insight into the mechanisms of\n                    <jats:italic>in vivo<\/jats:italic>\n                    iNOS dimer formation. UD dimers represent a class of iNOS dimers that had not been suspected. This unanticipated finding revises our understanding of the mechanisms of iNOS dimerization and lays the groundwork for future studies aimed at modulating iNOS activity\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.2435290100","type":"journal-article","created":{"date-parts":[[2003,11,25]],"date-time":"2003-11-25T15:59:06Z","timestamp":1069775946000},"page":"14263-14268","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":44,"title":["Intracellular formation of \u201dundisruptable\u201d dimers of inducible nitric oxide synthase"],"prefix":"10.1073","volume":"100","author":[{"given":"Pawel J.","family":"Kolodziejski","sequence":"first","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad B.","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Medicine, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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