Zinc-dependent metalloenzyme

Zinc-dependent metalloenzymes, encompassing families such as aminopeptidases and matrix metalloproteinases (MMPs), are a broad class of enzymes that utilize a zinc ion (Zn2+) as a critical catalytic or structural cofactor [1, 2]. These enzymes are essential for diverse biological functions, including the degradation and remodeling of the extracellular matrix, the processing of peptide hormones and antigens, and the regulation of gene expression through histone deacetylation [2, 4]. In various pathologies, the dysregulation of these enzymes plays a pivotal role; for example, overactive MMPs facilitate tumor metastasis and tissue destruction in inflammatory diseases, while aminopeptidases like ERAP1 are involved in autoimmune disorders [2, 4]. Because of their central roles in disease, they are major therapeutic targets for small-molecule inhibitors [3]. Most drugs targeting these enzymes function by coordinating with the active-site zinc ion to block catalytic activity [3, 5]. However, a significant challenge in drug development is achieving high selectivity, as broad-spectrum inhibition often leads to off-target effects and clinical toxicities, such as the musculoskeletal syndrome observed with early MMP inhibitors [4].

Other names

Zinc metalloenzymeZinc-dependent proteaseMetalloenzymeZinc-dependent hydrolaseAminopeptidasesMatrix metalloproteinases

Inhibition of catalytic activity by chelating or coordinating with the active site zinc ion, thereby preventing substrate hydrolysis or processing.