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We observed local rearrangements in the allosteric pocket upon BH4 binding, which result in drastic changes in the quaternary structure of the enzyme leading to a more compact, tense form in the inhibited protein. Inhibition of the enzymatic activity is not a result of hindrance of substrate binding, but rather a consequence of accelerated substrate binding kinetics as shown by STD-NMR and site-directed mutagenesis. 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