{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:56:07Z","timestamp":1788184567962,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T00:00:00Z","timestamp":1156464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p>\n                    Pterin\u20104a\u2010carbinolamine dehydratase (PCD) is an essential component of the phenylalanine hydroxylase (PAH) system, catalyzing the regeneration of the essential cofactor 6(R)\u2010L\u2010erythro\u20105,6,7,8\u2010tetrahydrobiopterin [6(R)BH\n                    <jats:sub>4<\/jats:sub>\n                    ]. Mutations in PCD or its deactivation by hydrogen peroxide result in the generation of 7(R,S)BH\n                    <jats:sub>4<\/jats:sub>\n                    , which is a potent inhibitor of PAH that has been implicated in primapterinuria, a variant form of phenylketonuria, and in the skin depigmentation disorder vitiligo. We have synthesized and separated the 7(R) and 7(S) diastereomers confirming their structure by NMR. Both 7(R)\u2010 and 7(S)BH\n                    <jats:sub>4<\/jats:sub>\n                    function as poor cofactors for PAH, whereas only 7(S)BH\n                    <jats:sub>4<\/jats:sub>\n                    acts as a potent competitive inhibitor\n                    <jats:italic>vs.<\/jats:italic>\n                    6(R)BH\n                    <jats:sub>4<\/jats:sub>\n                    (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    2.3\u20134.9 \u00b5M). Kinetic and binding studies, as well as characterization of the pterin\u2010enzyme complexes by fluorescence spectroscopy, revealed that the inhibitory effects of 7(R,S)BH\n                    <jats:sub>4<\/jats:sub>\n                    on PAH are in fact specifically based on 7(S)BH\n                    <jats:sub>4<\/jats:sub>\n                    binding. The molecular dynamics simulated structures of the pterin\u2010PAH complexes indicate that 7(S)BH\n                    <jats:sub>4<\/jats:sub>\n                    inhibition is due to its interaction with the polar region at the pterin binding site close to Ser\u2010251, whereas its low efficiency as cofactor is related to a suboptimal positioning toward the catalytic iron. 7(S)BH\n                    <jats:sub>4<\/jats:sub>\n                    is not an inhibitor for tyrosine hydroxylase (TH) in the physiological range, presumably due to the replacement of Ser\u2010251 by the corresponding Ala297. Taken together, our results identified structural determinants for the specific regulation of PAH and TH by 7(S)BH\n                    <jats:sub>4<\/jats:sub>\n                    , which in turn aid in the understanding of primapterinuria and acute vitiligo. \u2014Pey, A. L., Martinez, A., Charubala, R., Maitland, D. J., Teigen, K., Calvo, A., Pfleiderer, W., Wood, J. M., Schallreuter, K. U. Specific interaction of the diastereomers 7(R)\u2010 and 7(S)\u2010tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, E1451\u2013E1464 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-5835fje","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T22:50:47Z","timestamp":1156546247000},"page":"2130-2132","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Specific interaction of the diastereomers 7(R)\u2010 and 7(S)\u2010tetrahydrobiopterin with phenylalanine hydroxylase: implications for understanding primapterinuria and vitiligo"],"prefix":"10.1096","volume":"20","author":[{"given":"Angel L.","family":"Pey","sequence":"first","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramamurthy","family":"Charubala","sequence":"additional","affiliation":[{"name":"Fachbereich Chemie University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Maitland","sequence":"additional","affiliation":[{"name":"Departments of Chemical and Forensic Sciences Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Teigen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Pfleiderer","sequence":"additional","affiliation":[{"name":"Fachbereich Chemie University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin U.","family":"Schallreuter","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel L.","family":"Pey","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramamurthy","family":"Charubala","sequence":"additional","affiliation":[{"name":"Fachbereich Chemie University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Maitland","sequence":"additional","affiliation":[{"name":"Departments of Chemical and Forensic Sciences Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Knut","family":"Teigen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Pfleiderer","sequence":"additional","affiliation":[{"name":"Fachbereich Chemie University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin U.","family":"Schallreuter","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Dermatology\/Department of Biomedical Sciences University of Bradford Bradford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,8,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3470001"},{"key":"e_1_2_6_3_1","first-page":"1667","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Scriver C. 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