PAM Protein, Human (HEK293, Fc)

The PAM protein operates as a bifunctional enzyme, overseeing the post-translational modification of inactive peptidylglycine precursors to their bioactive alpha-amidated peptide forms—a crucial terminal modification in the biosynthesis of numerous neural and endocrine peptides. The alpha-amidation process involves two sequential reactions, each governed by distinct catalytic domains within the enzyme. In the first step, the peptidyl alpha-hydroxylating monooxygenase (PHM) domain catalyzes a copper-, ascorbate-, and O2-dependent stereospecific hydroxylation (with S stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate. The subsequent step, orchestrated by the peptidylglycine amidoglycolate lyase (PAL) domain, entails a zinc-dependent cleavage of the N-C-alpha bond, resulting in the production of the alpha-amidated peptide and glyoxylate. Additionally, PAM exhibits a similar capacity to catalyze the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate in a manner reminiscent of its peptidylglycine modification function.