Structure and Regulation of Phenylalanine Hydroxylase, and Implications for Related Enzymes

摘要: Phenylalanine hydroxylase (PAH) is a metabolic enzyme that converts Phe to Tyr using molecular oxygen, enzyme-bound iron, and 6R-tetrahydrobiopterin (BH4) cofactor (1, 2, 3). PAH member of the aromatic amino acid family, together with tyrosine (TH) tryptophan (TPH). TH TPH are involved in biosynthesis neurotransmitters, L-DOPA serotonin, respectively. The hydroxylases share similar mechanism have common three-domain structure consisting an N-terminal regulatory domain, catalytic domain C-terminal tetramerization domain; highest sequence structural similarity found domain. Over 300 different mutations gene been be associated disease phenylketonuria (PKU) (4), although only small proportion mutant proteins functionally characterised (5).