Zinc metalloenzyme

Zinc metalloenzymes are a diverse superfamily of enzymes that require Zn(II) ions for catalytic or structural roles, found in all six EC enzyme classes including hydrolases like carboxypeptidase and carbonic anhydrase, oxidoreductases like alcohol dehydrogenase, and lyases like aldolase.[1][3][5] The Zn center typically adopts distorted tetrahedral geometry coordinated by His, Cys, Asp, Glu, or water, enabling Lewis acid activation of substrates such as water for nucleophilic attack in hydrolysis or CO2 hydration.[1][3] These enzymes participate in critical processes like respiration (CO2 transport via carbonic anhydrase), protein degradation (carboxypeptidases), alcohol metabolism, DNA synthesis, cell proliferation, and apoptosis regulation.[2][3] Dysregulation links them to diseases: overexpressed carbonic anhydrases and matrix metalloproteinases (MMPs) in tumors promote invasion and acidosis, while histone deacetylases (HDACs) drive oncogenesis.[4] Therapeutics target the active site Zn, with inhibitors like acetazolamide for glaucoma (CA) or doxycycline for cancer metastasis (MMPs), though broad inhibition risks toxicity from disrupting Zn homeostasis.[1][2][4]

Other names

Zinc-containing enzymeZn enzymeZn metalloprotease (for subset)Zn hydrolase (for subset)

Inhibition of catalytic Zn-bound water activation (e.g., carbonic anhydrase); Chelation or displacement of active site Zn (e.g., matrix metalloproteinases); Hydroxamic acid coordination to Zn in HDACs; Displacement of Zn ligands like His/Cys/Asp/Glu