Glutaminyl-Peptide Cyclotransferase (QPCT), also known as glutaminyl cyclase (QC), is an enzyme that catalyzes the formation of pyroglutamate (pGlu) at the N-terminus of peptides and proteins. This post-translational modification is critical in various physiological processes, including protein maturation and stability. QPCT is involved in the pathogenesis of neurodegenerative diseases and amyloid plaque formation.

Technical Details

Structure:

• QPCT is a zinc-dependent enzyme belonging to the peptidase family.
• It has a catalytic domain responsible for the conversion of N-terminal glutamine residues into pyroglutamate.

Production:

• QPCT recombinant proteins are produced using recombinant DNA technology in systems such as E. coli, yeast, insect, or mammalian cells.
• Recombinant production ensures high purity and enzymatic activity, enabling detailed biochemical and functional studies.

Applications:

• Neurodegenerative Disease Research:
  • QPCT is implicated in the formation of amyloid-beta peptides in Alzheimer's disease.
  • Studying QPCT activity helps understand its role in amyloid plaque formation and neurotoxicity.
• Protein and Peptide Modification:
  • Investigating the role of pyroglutamate formation in protein maturation and function.
  • Studying the effects of QPCT-mediated modification on protein stability and activity.
• Drug Development:
  • Targeting QPCT for the development of inhibitors to prevent or reduce pyroglutamate formation.
  • Screening small molecules and peptides that inhibit QPCT activity, with potential therapeutic applications in neurodegenerative diseases.
• Biomarker Discovery:
  • Exploring QPCT levels and activity as biomarkers for disease diagnosis and progression, particularly in neurodegenerative and inflammatory conditions.

Analytical Methods:

• Enzyme Assays: To measure the catalytic activity of QPCT on peptide substrates.
• Mass Spectrometry: For detailed analysis of pyroglutamate formation and identification of modified peptides.
• Western Blotting: For detection and quantification of QPCT in biological samples.
• X-ray Crystallography and NMR: For structural analysis of QPCT and its interaction with substrates and inhibitors.