Document Type
Article
Publication Date
2016
Keywords
Cinnamate, cinnamate–Cu(I) complex, peptidylglycine α-hydroxylating monooxygenase, time-dependent enzyme inactivation
Digital Object Identifier (DOI)
https://doi.org/10.3109/14756366.2015.1046064
Abstract
Peptidylglycine α-amidating monooxygenase (PAM) is a bifunctional enzyme that catalyzes the final reaction in the maturation of α-amidated peptide hormones. Peptidylglycine α-hydroxylating monooxygenase (PHM) is the PAM domain responsible for the copper-, ascorbate- and O2-dependent hydroxylation of a glycine-extended peptide. Peptidylamidoglycolate lyase is the PAM domain responsible for the Zn(II)-dependent dealkylation of the α-hydroxyglycine-containing precursor to the final α-amidated peptide. We report herein that cinnamic acid and cinnamic acid analogs are inhibitors or inactivators of PHM. The inactivation chemistry exhibited by the cinnamates exhibits all the attributes of a suicide-substrate. However, we find no evidence for the formation of an irreversible linkage between cinnamate and PHM in the inactivated enzyme. Our data support the reversible formation of a Michael adduct between an active site nucleophile and cinnamate that leads to inactive enzyme. Our data are of significance given that cinnamates are found in foods, perfumes, cosmetics and pharmaceuticals.
Rights Information
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Enzyme Inhibition and Medicinal Chemistry, v. 31, issue 4, p. 551-562
This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Enzyme Inhibition and Medicinal Chemistry on 29 May 2015, available online: http://www.tandfonline.com/doi.org/10.3109/14756366.2015.1046064.
Scholar Commons Citation
McIntyre, Neil R.; Lowe, Edward W. Jr; Battistini, Matthew R.; Leahy, James W.; and Merkler, David J., "Inactivation of Peptidylglycine α-hydroxylating Monooxygenase by Cinnamic Acid Analogs" (2016). Chemistry Faculty Publications. 33.
https://digitalcommons.usf.edu/chm_facpub/33
