| Primary Identifier | IPR000720 | Type | Family |
| Short Name | PHM/PAL |
| description | 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 []. |
