Structural highlights
Function
[AMD_RAT] Bifunctional enzyme that catalyzes 2 sequential steps in C-terminal alpha-amidation of peptides. The monooxygenase part produces an unstable peptidyl(2-hydroxyglycine) intermediate that is dismutated to glyoxylate and the corresponding desglycine peptide amide by the lyase part. C-terminal amidation of peptides such as neuropeptides is essential for full biological activity.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Many neuropeptides and peptide hormones require amidation at the carboxyl terminus for activity. Peptidylglycine alpha-amidating monooxygenase (PAM) catalyzes the amidation of these diverse physiological regulators. The amino-terminal domain of the bifunctional PAM protein is a peptidylglycine alpha-hydroxylating monooxygenase (PHM) with two coppers that cycle through cupric and cuprous oxidation states. The anomalous signal of the endogenous coppers was used to determine the structure of the catalytic core of oxidized rat PHM with and without bound peptide substrate. These structures strongly suggest that the PHM reaction proceeds via activation of substrate by a copper-bound oxygen species. The mechanistic and structural insight gained from the PHM structures can be directly extended to dopamine beta-monooxygenase.
Amidation of bioactive peptides: the structure of peptidylglycine alpha-hydroxylating monooxygenase.,Prigge ST, Kolhekar AS, Eipper BA, Mains RE, Amzel LM Science. 1997 Nov 14;278(5341):1300-5. PMID:9360928[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Prigge ST, Kolhekar AS, Eipper BA, Mains RE, Amzel LM. Amidation of bioactive peptides: the structure of peptidylglycine alpha-hydroxylating monooxygenase. Science. 1997 Nov 14;278(5341):1300-5. PMID:9360928
