{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:32:22Z","timestamp":1790847142820,"version":"4.1.0"},"reference-count":82,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6135","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2013,5,24]]},"abstract":"<jats:title>Going Off-Target<\/jats:title>\n                  <jats:p>\n                    Sulfamethoxazole is a widely used sulfa-drug often used at high doses in the treatment of Pneumocytis pneumonia (PCP) in immunocompromised individuals.\n                    <jats:bold>\n                      Haruki\n                      <jats:italic>et al.<\/jats:italic>\n                    <\/jats:bold>\n                    (p.\n                    <jats:related-article xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" issue=\"6135\" page=\"987\" related-article-type=\"in-this-issue\" vol=\"340\" xlink:href=\"10.1126\/science.1232972\">987<\/jats:related-article>\n                    ) show that sulfamethoxazole and certain other sulfa drugs inhibit the enzyme septiapterin reductase that catalyzes the final step in the biosynthesis of tetrahydrobiopterin (BH4). BH4 is a cofactor in the biosynthesis of neurotransmitters such as serotonin and dopamine. In cell culture, sulfamethoxazole lowered neurotransmitter levels through depletion of BH4, which may explain central nervous system side effects associated with PCP treatment.\n                  <\/jats:p>","DOI":"10.1126\/science.1232972","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T14:20:19Z","timestamp":1369318819000},"page":"987-991","source":"Crossref","is-referenced-by-count":99,"title":["Tetrahydrobiopterin Biosynthesis as an Off-Target of Sulfa Drugs"],"prefix":"10.1126","volume":"340","author":[{"given":"Hirohito","family":"Haruki","sequence":"first","affiliation":[{"name":"EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research (NCCR) in Chemical Biology, 1015 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam Gr\u00f8nlund","family":"Pedersen","sequence":"additional","affiliation":[{"name":"EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research (NCCR) in Chemical Biology, 1015 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna Irena","family":"Gorska","sequence":"additional","affiliation":[{"name":"EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research (NCCR) in Chemical Biology, 1015 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Pojer","sequence":"additional","affiliation":[{"name":"\u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), Global Health Institute, 1015 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Johnsson","sequence":"additional","affiliation":[{"name":"EPFL, Institute of Chemical Sciences and Engineering, Institute of Bioengineering, National Centre of Competence in Research (NCCR) in Chemical Biology, 1015 Lausanne, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20110293"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22685"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.08.017"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.557"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.24.7219"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21447"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp953141+"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/321970"},{"key":"e_1_3_2_10_2","unstructured":"T. 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