Ubiquitin and ubiquitin-derived peptides as substrates for peptidylglycine alpha-amidating monooxygenase.
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.
Chew
Geoffrey H
GH
Department of Chemistry, University of South Florida, 4202 E. Fowler Ave., SCA 400, Tampa, FL 33620-5250, USA.
Galloway
Lamar C
LC
McIntyre
Neil R
NR
Schroder
Laura Aaron
LA
Richards
Karla M
KM
Miller
Scott A
SA
Wright
David W
DW
Merkler
David J
DJ
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*
D006038:Glyoxylates; D009097:Multienzyme Complexes; D010455:Peptides; D025801:Ubiquitin; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; C031150:glyoxylic acid; D010100:Oxygen; D005998:Glycine