Zinc metallopeptidase

Zinc metallopeptidases are a large and diverse group of zinc-dependent enzymes that hydrolyze peptide bonds in proteins and peptides[1][4][7]. They rely on a zinc ion coordinated in the active site, typically through a conserved HEXXH motif, for catalytic activity[4][7]. Members—including neprilysin (neutral endopeptidase), angiotensin-converting enzyme (ACE), and neurolysin—play essential physiological roles in controlling the levels of neuropeptides, peptide hormones, and regulatory peptides in extracellular and intracellular spaces[1][10]. The deregulation of zinc metallopeptidase activity has been linked to diseases including cancer, cardiovascular disorders, and neurodegeneration, especially Alzheimer's disease, where neprilysin mediates amyloid-beta degradation[1][6]. These enzymes are classified into several families (e.g., M7, M8, M10, M12, M13), organized in umbrella clans such as metzincins and gluzincins, based on structural and sequence similarities[2][4][5][7]. Clinically, zinc metallopeptidases are therapeutically targeted by ACE inhibitors in hypertension and neprilysin inhibitors in heart failure[1][6]. While “zinc metallopeptidases” is a valid functional class, for drug discovery or biomarker purposes, it is important to specify the precise family or individual enzyme due to the diversity of this superfamily[4][7][8].

Other names

MetalloproteaseMetallopeptidaseMetal-dependent peptidaseZincinGluzincinMetzincinNeutral endopeptidaseAngiotensin-converting enzymeNeprilysin

Inhibition of enzymatic peptide cleavage; Modulation of peptide signaling pathways; Blockade of neuropeptide and angiotensin metabolism