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Báo cáo khoa học: Studies on the regulatory properties of the pterin cofactor and dopamine bound at the active site of human phenylalanine hydroxylase

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The catalytic activity of phenylalanine hydroxylase (PAH,phenylalanine 4-monooxygenase EC 1.14.16.1) is regulatedby three main mechanisms, i.e. substrate (L-phenylalanine,L-Phe) activation, pterin cofactor inhibition and phos-phorylation of a single serine (Ser16) residue.To address themolecular basis for the inhibition by the natural cofactor(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, its effects on therecombinant tetrameric human enzyme (wt-hPAH) wasstudied using three different conformational probes, i.e. thelimited proteolysis by trypsin, the reversible global con-formational transition (hysteresis) triggered by L-Phe bind-ing, as measured in real time by surface plasmon resonanceanalysis, and the rateof phosphorylationof Ser16bycAMP-dependent protein kinase....
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Báo cáo khoa học: Studies on the regulatory properties of the pterin cofactor and dopamine bound at the active site of human phenylalanine hydroxylase

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