Glutaminyl cyclases display significant catalytic proficiency for glutamyl substrates

Biochemistry. 2009 Dec 22;48(50):11831-3. doi: 10.1021/bi9018835.


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.

MeSH terms

  • Alzheimer Disease / enzymology
  • Alzheimer Disease / physiopathology
  • Aminoacyltransferases / chemistry*
  • Aminoacyltransferases / metabolism
  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Animals
  • Catalysis
  • Cyclization
  • Glutamine / chemistry*
  • Glutamine / metabolism
  • Humans
  • Substrate Specificity


  • Amyloid
  • Glutamine
  • Aminoacyltransferases
  • glutaminyl-peptide cyclotransferase