{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:46:58Z","timestamp":1760150818528,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["DOTSUT-34\/09.3.3-LMT-K712-01-0058"],"award-info":[{"award-number":["DOTSUT-34\/09.3.3-LMT-K712-01-0058"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuronal nitric oxide synthase (nNOS) catalyzes single-electron reduction of quinones (Q), nitroaromatic compounds (ArNO2) and aromatic N-oxides (ArN \u2192 O), and is partly responsible for their oxidative stress-type cytotoxicity. In order to expand a limited knowledge on the enzymatic mechanisms of these processes, we aimed to disclose the specific features of nNOS in the reduction of such xenobiotics. In the absence or presence of calmodulin (CAM), the reactivity of Q and ArN \u2192 O increases with their single-electron reduction midpoint potential (E17). ArNO2 form a series with lower reactivity. The calculations according to an \u201couter-sphere\u201d electron transfer model show that the binding of CAM decreases the electron transfer distance from FMNH2 to quinone by 1\u20132 \u00c5. The effects of ionic strength point to the interaction of oxidants with a negatively charged protein domain close to FMN, and to an increase in accessibility of the active center induced by high ionic strength. The multiple turnover experiments of nNOS show that, in parallel with reduced FAD-FMN, duroquinone reoxidizes the reduced heme, in particular its Fe2+-NO form. This finding may help to design the heme-targeted bioreductively activated agents and contribute to the understanding of the role of P-450-type heme proteins in the bioreduction of quinones and other prooxidant xenobiotics.<\/jats:p>","DOI":"10.3390\/ijms23020980","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T08:20:42Z","timestamp":1642407642000},"page":"980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reactions of Recombinant Neuronal Nitric Oxide Synthase with Redox Cycling Xenobiotics: A Mechanistic Study"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3069-5734","authenticated-orcid":false,"given":"Mindaugas","family":"Lesanavi\u010dius","sequence":"first","affiliation":[{"name":"Department of Xenobiotics Biochemistry, Institute of Biochemistry of Vilnius University, Saul\u0117tekio 7, LT-10257 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Luc","family":"Boucher","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie & Biochimie Pharmacologiques et Toxicologiques, CNRS UMR 8601, Universit\u00e9 Paris Descartes, 45 rue de Saints P\u00e8res, CEDEX 06, 75270 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narimantas","family":"\u010c\u0117nas","sequence":"additional","affiliation":[{"name":"Department of Xenobiotics Biochemistry, Institute of Biochemistry of Vilnius University, Saul\u0117tekio 7, LT-10257 Vilnius, Lithuania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"ref_1","unstructured":"Ignarro, L.J., and Freeman, B.A. (2017). 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