{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T04:31:08Z","timestamp":1773117068795,"version":"3.50.1"},"reference-count":49,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,14]]},"abstract":"<jats:p>The pro-oxidant effect of free heme (Fe2+-protoporphyrin IX) is neutralized by phylogenetically-conserved heme oxygenases (HMOX) that generate carbon monoxide, free ferrous iron, and biliverdin (BV) tetrapyrrole(s), with downstream BV reduction by non-redundant NADPH-dependent BV reductases (BLVRA and BLVRB) that retain isomer-restricted functional activity for bilirubin (BR) generation. Regioselectivity for the heme \u03b1-meso carbon resulting in predominant BV IX\u03b1 generation is a defining characteristic of canonical HMOXs, thereby limiting generation and availability of BVs IX\u03b2, IX\u03b4, and IX\u03b3 as BLVRB substrates. We have now exploited the unique capacity of the Pseudomonas aeruginosa (P. aeruginosa) hemO\/pigA gene for focused generation of isomeric BVs (IX\u03b2 and IX\u03b4). A scalable system followed by isomeric separation yielded highly pure samples with predicted hydrogen-bonded structure(s) as documented by 1H NMR spectroscopy. Detailed kinetic studies established near-identical activity of BV IX\u03b2 and BV IX\u03b4 as BLVRB-selective substrates, with confirmation of an ordered sequential mechanism of BR\/NADP+ dissociation. Halogenated xanthene-based compounds previously identified as BLVRB-targeted flavin reductase inhibitors displayed comparable inhibition parameters using BV IX\u03b2 as substrate, documenting common structural features of the cofactor\/substrate-binding pocket. These data provide further insights into structure\/activity mechanisms of isomeric BVs as BLVRB substrates, with potential applicability to further dissect redox-regulated functions in cytoprotection and hematopoiesis.<\/jats:p>","DOI":"10.1042\/bcj20190810","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T11:56:41Z","timestamp":1580990201000},"page":"601-614","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biochemical characterization of biliverdins IX\u03b2\/\u03b4 generated by a selective heme oxygenase"],"prefix":"10.1042","volume":"477","author":[{"given":"Beibei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, U.S.A."}]},{"given":"Natasha M.","family":"Nesbitt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook University, Stony Brook, NY 11797, U.S.A."}]},{"given":"Pedro Jos\u00e9 Barbosa","family":"Pereira","sequence":"additional","affiliation":[{"name":"IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-8503","authenticated-orcid":false,"given":"Wadie F.","family":"Bahou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook University, Stony Brook, NY 11797, U.S.A."}]}],"member":"288","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"key":"2021112218050676700_BCJ-2019-0810C1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1124\/pr.107.07104","article-title":"Pharmacological and clinical aspects of heme oxygenase","volume":"60","year":"2008","journal-title":"Pharmacol. 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