Biosynthesis of pteridines. NMR studies on the reaction mechanisms of GTP cyclohydrolase I, pyruvoyltetrahydropterin synthase, and sepiapterin reductase |
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Authors: | A Bracher W Eisenreich N Schramek H Ritz E G?tze A Herrmann M Gütlich A Bacher |
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Affiliation: | Institut für Organische Chemie und Biochemie, Technische Universit?t München, Lichtenbergstrasse 4, D-85747 Garching, Federal Republic of Germany. Bacher@oc3gra.org.chemie |
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Abstract: | GTP cyclohydrolase I catalyzes a ring expansion affording dihydroneopterin triphosphate from GTP. 1',2',3',4',5'-13C5, 2'-2H1]GTP was prepared enzymatically from U-13C6]glucose for use as enzyme substrate. Multinuclear NMR experiments showed that the reaction catalyzed by GTP cyclohydrolase I involves the release of a proton from C-2' of GTP that is exchanged with the bulk solvent. Subsequently, a proton is reintroduced stereospecifically from the bulk solvent. This is in line with an Amadori rearrangement mechanism. The proton introduced from solvent occupies the pro-7R position in the enzyme product. The data also confirm that the reaction catalyzed by pyruvoyltetrahydropterin synthase results in the incorporation of solvent protons into positions C-6 and C-3' of the enzyme product. On the other hand, the reaction catalyzed by sepiapterin reductase does not involve any detectable incorporation of solvent protons into tetrahydrobiopterin. |
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