PAM/Peptidyl-glycine alpha-amidating monooxygenase
Function
Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (PubMed:12699694). Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monooxygenase (PHM) domain, is the 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 (PubMed:12699694). The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (PubMed:12699694). Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (By similarity).
Sequence Similarities
In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family.
In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.
Cellular localization
- Cytoplasmic vesicle
- Secretory vesicle membrane
- Single-pass membrane protein
- Secretory granules.
- Isoform 1
- Membrane
- Single-pass type I membrane protein
- Isoform 2
- Membrane
- Single-pass type I membrane protein
- Isoform 3
- Secreted
- Secreted from secretory granules.
- Isoform 4
- Secreted
- Secreted from secretory granules.
Alternative names
Peptidyl-glycine alpha-amidating monooxygenase, PAM