The catalytic activity of phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase EC ) is regulated by three main mechanisms, . substrate (L-phenylalanine, L-Phe) activation, pterin cofactor inhibition and phos-phorylation of a single serine (Ser16) address the molecular basis for the inhibition by the natural cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin, its effects on the recombinant tetrameric human enzyme (wt-hPAH) was studied using three different conformational probes, . the limited proteolysis by trypsin, the reversible global con-formational transition (hysteresis) triggered by L-Phe bind-ing, as measured in real time by surface plasmon resonance analysis, and the rateof phosphorylationof Ser16bycAMP-dependent protein kinase
