title: Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha-amidating monooxygenase.
abstract: Ubiquitin (Ub) and the ubiquitin-like proteins (UBLs) mediate an array of cellular functions. These proteins contain a C-terminal glycine residue that is key to their function. Oxidative conversion of C-terminal glycine-extended prohormones to the corresponding alpha-amidated peptide is one step in the biosynthesis of bioactive peptide hormones. The enzyme catalyzing this reaction is peptidylglycine alpha-amidating monooxygenase (PAM). We report herein that Ub is a PAM substrate with a (V/K)(amidation) that is similar to other known peptide substrates. This work is significant because PAM and the UBLs co-localize to the hypothalamus and the adrenal medulla and are both over-expressed in glioblastomas.
authors.affiliation: Department of Chemistry, University of South Florida, 4202 E. Fowler Ave., SCA 400, Tampa, FL 33620-5250, USA.
authors.forename: Geoffrey H
authors.initials: GH
authors.lastname: Chew
authors.forename: Lamar C
authors.initials: LC
authors.lastname: Galloway
authors.forename: Neil R
authors.initials: NR
authors.lastname: McIntyre
authors.forename: Laura Aaron
authors.initials: LA
authors.lastname: Schroder
authors.forename: Karla M
authors.initials: KM
authors.lastname: Richards
authors.forename: Scott A
authors.initials: SA
authors.lastname: Miller
authors.forename: David W
authors.initials: DW
authors.lastname: Wright
authors.forename: David J
authors.initials: DJ
authors.lastname: Merkler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D005998:Glycine / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: D006038:Glyoxylates; D009097:Multienzyme Complexes; D010455:Peptides; D025801:Ubiquitin; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; C031150:glyoxylic acid; D010100:Oxygen; D005998:Glycine