Succinimide formation from aspartyl and asparaginyl
peptides as a model for the spontaneous degradation of proteins.
Legumain (LGMN) also known as asparaginyl
endopeptidase (AEP) is implicated in various cancer such as prostrate, breast, colon, lung, ovarian, central nervous system (CNS) related cancers, melanoma and lymphoma (1).
Amarnaths team investigated how PD-1 blocked these cancer fighting cells; they found that PD-1 specifically downregulated a new enzyme called asparaginyl
endopeptidase (AEP) which was key to shifting the balance between cancer fighting cells and regulatory T cells within the melanoma tumour environment.
The most common is Jo-1 (histidyl) (15%-30% prevalence), followed by PL-7 (threonyl) and PL-12 (alanyl), with a prevalence of 5% to 10%, followed by EJ (glycyl), OJ (isoleucyl), KS (asparaginyl
), Zo (phenylalanyl), and YRS (tyrosyl) (all with prevalences of 1%-5%).
Schachner, "The asparaginyl
endopeptidase legumain is essential for functional recovery after spinal cord injury in adult zebrafish," PLoS One, vol.
LGMN, legumain, has a strict specificity for hydrolysis of asparaginyl
bonds required for normal lysosomal protein degradation in renal proximal tubules and plays a role in the regulation of cell proliferation via its role in EGFR degradation; VDR, vitamin D (1,25-dihydroxyvitamin D3), is a nuclear receptor that mediates the action of vitamin D3 by controlling the expression of hormone-sensitive genes and plays a central role in calcium homeostasis; HP, haptoglobin, captures and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage.
Morgenstern et al., "A radiolabeled fully human antibody to human aspartyl (asparaginyl
) jhydroxylase is a promising agent for imaging and therapy of metastatic breast cancer," Cancer Biotherapy & Radiopharmaceuticals, vol.
Houk, "Neighboring side chain effects on asparaginyl
and aspartyl degradation: an Ab initio study of the relationship between peptide conformation and backbone NH acidity," Journal of the American Chemical Society, vol.
Kinetics of deamidation of an asparaginyl
residue in a model hexapeptide." Pharmaceutical Research 7, (1990): 703-711
Deamidation of glutaminyl and asparaginyl
residues in peptides and proteins.
Proteomics-based identification of novel factor inhibiting hypoxia-inducible factor (FIH) substrates indicates widespread asparaginyl
hydroxylation of ankyrin repeat domain-containing proteins.
Transient metal ions like nickel and cobalt are known to mimic cellular hypoxia mainly due to the inhibition of prolyl hydrolases (PDHs) and asparaginyl
hydrolase (factor-inhibiting HIF (FIH)).