Peptidylglycine a-amidating enzyme

Francisco, W. A., Merkler, D. J., Blackburn, N. J., Klinman, J. P. (1998) Kinetic mechanism and intrinsic isotope effects for the peptidylglycine a-amidating enzyme reaction. Biochemistry 37, 8244-8252. 

A similar copper-dependent hydroxylase constitutes the N-terminal domain of the peptidylglycine a-amidating enzyme (Eq. 10-11). This bifunctional enzyme hydroxylates C-terminal glycines in a group of neuropeptide hormones and other secreted peptides. The second functional domain of the enzyme cleaves the hydroxylated glycine to form a C-terminal... 

The PHM domain in peptidylglycine a-amidating enzyme shows 28% sequence identity to part of the amino acid sequence in D/3M. As described below, the spectroscopic and redox properties of the copper ions in D/3M and PHM are also highly similar. Hence, although crystallographic data are only available for PHM, the active site structures and catalytic mechanisms of D/3M and PHM are assumed to be similar. For this reason, they will be discussed together. 

Boswell JS, Reedy BJ, Kulathila R, Merkler D, Blackburn NJ. 1996. Structural investigations on the coordination environment of the active site copper centers of recombinant bifunctional peptidylglycine a-amidating enzyme. Biochemistry 35 12241-12250. 

Peptidylglycine monooxygenase [EC 1.14.17.3], also known as peptidyl a-amidating enzyme and peptidylglycine 2-hydroxylase, catalyzes the reaction of a peptidylglycine with ascorbate and dioxygen to produce a pepti-dyl(2-hydroxyglycine), dehydroascorbate, and water. 

Kolhekar, A., Mains, R. W., and Eipper, B. A. (1997), Peptidylglycine a-amidating monoooxygenase An ascorbate-requiring enzyme. Methods Enzipnot. 279, Part 1,35-43. 

FIGURE 10.38 Distribution of markers in pancreatic endocrine tumors. SYN, synaptophysin NSE, neuron-specific enolase LMWCK, low-molecular-weight cytokeratin CgA, chromogranin A PC2, pro-convertase 2 PCM, peptidylglycine alpha-amidating enzyme PC3, proconvertase 3 NFP, neurofilament protein HCC(a), human chorionic gonadotropin alpha VIM, vimentin. 

Amidation, the formation of amides. Amino acid and peptide amides are synthesized by reaction of the appropriate esters or activated carboxylic acid derivatives with ammonia. Amidation of bioactive peptides is performed using the bifunctional enzyme peptidylglycine a-amidating monooxygenase (PAM) by N-oxidative cleavage of a glycine-extended precursor [S. T. Prigge et al.. Science 1997, 278, 1300]. 

A number of peptide hormones have a carboxyl terminal amide which is derived from a glycine terminal residue. This glycine is hydroxylated on the a-carbon by a copper-containing enzyme, peptidylglycine hydroxylase, which, again, requires ascorbate for reduction of Cu ". ... 

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