Glutaminyl cyclases display significant catalytic proficiency for glutamyl substrates.
N-Terminal glutaminyl and glutamyl residues of peptides and proteins tend to form pyroglutamic acid (pGlu) by intramolecular cylization. The rate constants for spontaneous cyclization of glutamine (10(-6) s(-1)) and glutamic acid (10(-9) s(-1)) in aqueous solution differ by approximately 3 orders of magnitude at pH 6.5. Glutaminyl cyclases (QCs) from plants and mammals accelerate pGlu formation. Human QC exhibits a rate enhancement of 2.2 x 10(5) for glutamate cyclization, approximately 2 orders of magnitude lower than that of the corresponding N-terminal glutaminyl reaction. Thus, glutaminyl cyclases are enzymes with only modest specificity for cyclization of their primary glutaminyl substrates and may provide a link between glutamate cyclization and pathophysiology.
Seifert
Franziska
F
Probiodrug AG, Weinbergweg 22, 06120 Halle, Germany.
Schulz
Katrin
K
Koch
Birgit
B
Manhart
Susanne
S
Demuth
Hans-Ulrich
HU
Schilling
Stephan
S
D000544:Alzheimer Disease / Q000201:enzymology / Q000503:physiopathology; D019881:Aminoacyltransferases / Q000737:chemistry* / Q000378:metabolism; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D003500:Cyclization; D005973:Glutamine / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D013379:Substrate Specificity
D000682:Amyloid; D005973:Glutamine; D019881:Aminoacyltransferases; C059280:glutaminyl-peptide cyclotransferase