Nonheme mono- and dioxygenases

Nonheme mono- and dioxygenases are iron-dependent enzymes that oxygenate substrates using molecular oxygen as oxygen donor. They catalyze a wide range of reactions in which the electrons needed for the oxygen activation are provided by the substrate or by the substrate and a co-substrate. Phenylalanine hydroxylase is the most studied of the pterin-dependent monoxygenases since mutations in its sequence are responsible for phenylketonuria, a misfolding genetic disorder. Pharmacological chaperones stabilizing the enzyme are currently under investigation for the cure of phenylketonuria. 3-Hydroxyanthranilate 3,4-dioxygenase is a cupin ring cleaving dioxygenase that in humans is involved in the kynureine pathway and is a promising drug target for neurodegenerative diseases, including ALS. 4-Hydroxyphenylpyruvate 1,2-dioxygenase catalyzes the second step of the tyrosine pathway and belong to the 2-oxoglutarate-dependent dioxygenase family. Nitisinone, a triketon based inhibitor, is an approved drug for the treatment of Alkaptonuria and type I tyrosinemia, two disorders related to the tyrosine catabolism.