caa a22 4500 475845706 CHVBK 20180406123913.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/PL00000763 doi (NATIONALLICENCE)springer-10.1007/PL00000763 New insights into copper monooxygenases and peptide amidation: structure, mechanism and function [Elektronische Daten] [S. T. Prigge, R. E. Mains, B. A. Eipper, L. M. Amzel* **] Abstract.: Many bioactive peptides must be amidated at their carboxy terminus to exhibit full activity. Surprisingly, the amides are not generated by a transamidation reaction. Instead, the hormones are synthesized from glycine-extended intermediates that are transformed into active amidated hormones by oxidative cleavage of the glycine N-Cα bond. In higher organisms, this reaction is catalyzed by a single bifunctional enzyme, peptidylglycine α-amidating monooxygenase (PAM). The PAM gene encodes one polypeptide with two enzymes that catalyze the two sequential reactions required for amidation. Peptidylglycine α-hydroxylating monooxygenase (PHM; EC 1.14.17.3) catalyzes the stereospecific hydroxylation of the glycine α-carbon of all the peptidylglycine substrates. The second enzyme, peptidyl-α-hydroxyglycine α-amidating lyase (PAL; EC 4.3.2.5), generates α-amidated peptide product and glyoxylate. PHM contains two redox-active copper atoms that, after reduction by ascorbate, catalyze the reduction of molecular oxygen for the hydroxylation of glycine-extended substrates. The structure of the catalytic core of rat PHM at atomic resolution provides a framework for understanding the broad substrate specificity of PHM, identifying residues critical for PHM activity, and proposing mechanisms for the chemical and electron-transfer steps in catalysis. Since PHM is homologous in sequence and mechanism to dopamine β-monooxygenase (DBM; EC 1.14.17.1), the enzyme that converts dopamine to norepinephrine during catecholamine biosynthesis, these structural and mechanistic insights are extended to DBM. Birkhäuser Verlag Basel,, 2000 Key words. Amidation nationallicence copper nationallicence peptidylglycine α-amidating monooxygenase nationallicence dopamine β-monooxygenase nationallicence electron transfer nationallicence structure nationallicence ascorbate nationallicence peptide hormones nationallicence oxygen chemistry nationallicence Prigge S. T. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut Mains R. E. Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut Eipper B. A. Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut Amzel* ** L. M. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut https://doi.org/10.1007/PL00000763 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00000763 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Prigge S. T. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut NATIONALLICENCE 700 1- Mains R. E. Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut NATIONALLICENCE 700 1- Eipper B. A. Departments of Neuroscience and Physiology, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut NATIONALLICENCE 700 1- Amzel* ** L. M. Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore (Maryland 21205, USA), US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer