M1 family aminopeptidases (M1 aminopeptidases)

The M1 family of aminopeptidases consists of zinc-dependent metalloenzymes that play a pivotal role in the hydrolysis of N-terminal amino acids from various peptide and protein substrates (Rawlings et al., 2018, Nucleic Acids Res). These enzymes, which include prominent members like Aminopeptidase N (CD13) and Endoplasmic Reticulum Aminopeptidases (ERAP1 and ERAP2), are essential for physiological processes such as the final stages of protein catabolism, blood pressure control through the renin-angiotensin system, and the trimming of peptides for MHC class I antigen presentation (Luan and Xu, 2007, Curr Med Chem; Stratikos et al., 2006, Curr Drug Targets). In clinical contexts, M1 aminopeptidases are frequently associated with cancer progression, where they facilitate tumor cell invasion, migration, and angiogenesis (Wickström et al., 2011, Cancer Sci). Furthermore, they are implicated in inflammatory, cardiovascular, and infectious diseases, such as malaria, where the Plasmodium falciparum M1 aminopeptidase is a validated drug target (Drinkwater et al., 2017, Biochem J). Consequently, they have emerged as significant therapeutic targets, with inhibitors like Bestatin and Tosedostat being explored for their ability to disrupt catalytic activity by coordinating with the active-site zinc ion (Ota, 1991, Biotherapy). Selective inhibition of specific family members remains a key challenge in developing effective treatments with minimal side effects (Mistry et al., 2013, J Med Chem).

Other names

MEROPS family M1Zinc-dependent aminopeptidasesAlanyl aminopeptidase familyGluzincins

Inhibition of the catalytic zinc-dependent active site, typically through coordination with the zinc ion by a hydroxamate, phosphonate, or thiol group, thereby preventing the cleavage of N-terminal amino acids from peptide substrates (Rawlings et al., 2018, Nucleic Acids Res).