Peptidylglycine amidating monooxygenase
The catalytic core of PHM consists of two β-clamshell or sandwich domains.Each approximately 150-amino acid domain contains a single copper binding site. The two domains are held together by a single hydrophilic linker strand, whereas the interiors of the domains are very hydrophobic.At alkaline p H, the lyase reaction occurs spontaneously.The first A key step in the development of an assay for the biosynthesis of α-amidated peptides came from the sequencing of c DNAs encoding peptide precursors and the realization that α-amidated peptides were always derived from peptidylglycine precursors (.Based on sequence similarity, two additional potential family members, monooxygenase X and dopamine-β-hydroxylase-L, have been identified; their substrate specificity has not been determined. However, of the amino acid residues that are conserved among species, site-directed mutagenesis has identified a subset that are candidates for involvement in maintaining the structure of PAL and additional residues that are candidates for involvement in the PAL catalytic mechanism.
From: The two enzymatic activities necessary to perform the peptide α-amidation reaction are initially synthesized as a single bifunctional precursor protein called peptidylglycine-α-amidating monooxygenase (PAM) (). Alternative splicing generates several forms of PAM that differ in important ways.
It was shown that the purified enzyme had converted the model peptide to the C-terminal alpha-hydroxyglycine-extended peptide [X-Gly(OH)] instead of the amidated product (X-NH2), indicating that the enzyme widely known as ' PAM' should be called 'peptidylglycine alpha-hydroxylating monooxygenase'.