F
IPR000720

Peptidylglycine alpha-hydroxylating monooxygenase/peptidyl-hydroxyglycine alpha-amidating lyase

InterPro entry
Short namePHM/PAL
Overlapping
homologous
superfamilies
 

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
[1, 2]
:

peptidylglycine + ascorbate + O2 = peptidyl-(2-hydroxyglycine) + dehydroascorbate + H2O

The 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
[2]
.

References

1.Characterization of novel mRNAs encoding enzymes involved in peptide alpha-amidation. Stoffers DA, Ouafik L, Eipper BA. J. Biol. Chem. 266, 1701-7, (1991). View articlePMID: 1988445

2.The multifunctional peptidylglycine alpha-amidating monooxygenase gene: exon/intron organization of catalytic, processing, and routing domains. Ouafik LH, Stoffers DA, Campbell TA, Johnson RC, Bloomquist BT, Mains RE, Eipper BA. Mol. Endocrinol. 6, 1571-84, (1992). View articlePMID: 1448112

Further reading

3. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Prigge ST, Mains RE, Eipper BA, Amzel LM. Cell. Mol. Life Sci. 57, 1236-59, (2000). View articlePMID: 11028916

4. The copper-enzyme family of dopamine beta-monooxygenase and peptidylglycine alpha-hydroxylating monooxygenase: resolving the chemical pathway for substrate hydroxylation. Klinman JP. J. Biol. Chem. 281, 3013-6, (2006). View articlePMID: 16301310

5. PHM is required for normal developmental transitions and for biosynthesis of secretory peptides in Drosophila. Jiang N, Kolhekar AS, Jacobs PS, Mains RE, Eipper BA, Taghert PH. Dev. Biol. 226, 118-36, (2000). View articlePMID: 10993678

6. Drosophila uses two distinct neuropeptide amidating enzymes, dPAL1 and dPAL2. Han M, Park D, Vanderzalm PJ, Mains RE, Eipper BA, Taghert PH. J. Neurochem. 90, 129-41, (2004). View articlePMID: 15198673

GO terms

Cross References

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