Amidation of bioactive peptides: The structure of peptidylglycine α- hydroxylating monooxygenase

Sean T. Prigge, Aparna S. Kolhekar, Betty A. Eipper, Richard E. Mains, L. Mario Amzel

Research output: Contribution to journalArticlepeer-review

Abstract

Many neuropeptides and peptide hormones require amidation at the carboxyl terminus for activity. Peptidylglycine α-amidating monooxygenase (PAM) catalyzes the amidation of these diverse physiological regulators. The amino-terminal domain of the bifunctional PAM protein is a peptidylglycine α-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 β- monooxygenase.

Original languageEnglish (US)
Pages (from-to)1300-1305
Number of pages6
JournalScience
Volume278
Issue number5341
DOIs
StatePublished - Nov 14 1997

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Amidation of bioactive peptides: The structure of peptidylglycine α- hydroxylating monooxygenase'. Together they form a unique fingerprint.

Cite this