This entry includes tyramine beta-hydroxylases from invertebrates and dopamine beta-hydroxylases from mammals. Tyramine beta-hydroxylase (TBH) converts tyramine into octopamine, a neurotransmitter involved in pharyngeal pumping and egg laying in Caenorhabditis elegans []and in ovulation and locomotion in Drosophila [, , ]. It is evolutionarily related and remarkably similar to mammalian dopamine beta-hydroxylase [].Dopamine beta-hydroxylases (DBH) converts dopamine to noradrenaline (norepinephrine), a key neurotransmitter of the central and peripheral nervous systems [, ]. DBH is a copper-containing oxygenase consisting of four identical subunits. Mutations in DBH gene cause the dopamine beta-hydroxylase deficiency (DBH deficiency), which is characterised by profound deficits in autonomic and cardiovascular function [].
This family represents Dopamine beta-hydroxylase (DBH) and related enzymes, including tyramine beta-hydroxylase, MOXD1 homologue 1/2 and DBH-like monooxygenase protein 1/2 [].DBH, also known as Dopamine beta-hydroxylase, is a class of ascorbate-dependent enzymes from the catecholamine biosynthetic pathway that requires copper as a cofactor and uses ascorbate as an electron donor. DBH catalyses the conversion of dopamine to the neurotransmitter norepinephrine:3,4-dihydroxyphenethylamine+ ascorbate + O2= noradrenaline + dehydroascorbate + H2ODBH exists in both soluble (in chromaffin granules) and membrane bound forms. The protein functions as a homotetramer [, ].This entry includes monooxigenases found in metazoans, plants and fungi.
This DOMON domain can be found in dopamine beta-hydroxylase (DBH), monooxygenase X (MOX), and various other proteins, some of which contain DOMON domains exclusively. DBH is a membrane-bound enzyme that converts dopamine to L-norepinephrine, and plays a central role in the metabolism of catecholamine neurotransmitters [, ]. DOMON domains were initially thought to confer protein-protein interactions. They were subsequently found as a heme-binding motif in cellobiose dehydrogenase, an extracellular fungal oxidoreductase that degrades both lignin and cellulose, and in ethylbenzene dehydrogenase, an enzyme that aids in the anaerobic degradation of hydrocarbons. The domain interacts with sugars in the type 9 carbohydrate binding modules (CBM9), which are present in a variety of glycosyl hydrolases, and it can also be found at the N terminus of sensor histidine kinases [, ].
In vertebrates, peptidylglycine alpha-amidating monooxygenase (PAM) is a multifunctional protein found in secretory granules. The protein contains two enzymes, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), that act sequentially to catalyse the alpha-amidation of neuroendocrine peptides [, ]: peptidylglycine + ascorbate + O2= peptidyl-(2-hydroxyglycine) + dehydroascorbate + H2OThe product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide. The first step of the reaction is catalysed by peptidylglycine alpha-hydroxylating monooxygenase (PHM), and is dependent on copper, ascorbate and molecular oxygen; peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) catalyses the second step of the reaction []. PHM share protein sequence similarity with dopamine-beta-monooxygenases (DBH), a class of ascorbate-dependent enzymes that requires copper as a cofactor and uses ascorbate as an electron donor. PHM and DBH share a few regions of sequence similarity, some of which contain clusters of conserved histidine residues that may be involved in copper binding [, ].Interestingly, in Drosophila, the PHM and PAL enzyme are not fused. The Drosophila genome predicts expression of one monofunctional PHM gene and two monofunctional PAL genes []. Drosophila PHM encodes an active enzyme that is required for peptide amidation in vivo [], while both PAL proteins display PAL enzymatic activity and are involved in neuroendocrine biosynthesis [].
