Metalloproteins (Copper and Zinc-dependent)

Metalloproteins requiring copper (Cu) and zinc (Zn) constitute a significant class of therapeutic targets involved in a wide array of physiological processes (Source: NCBI, PMC2844821). Zinc-dependent enzymes, such as carbonic anhydrases and matrix metalloproteinases (MMPs), utilize the Lewis acid properties of the Zn2+ ion to catalyze hydration reactions or peptide bond hydrolysis, making them key targets in glaucoma and cancer therapy (Source: StatPearls, NBK541081). Copper-dependent enzymes, including superoxide dismutase (SOD1) and lysyl oxidase, are essential for managing oxidative stress and cross-linking extracellular matrix proteins, with implications in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and fibrotic conditions (Source: UniProt, P00441). Pharmacological intervention typically involves small molecules with metal-binding groups, such as sulfonamides or hydroxamates, that coordinate directly with the metal center to inhibit enzymatic activity (Source: PubChem). However, targeting these proteins requires high selectivity to avoid disrupting the systemic homeostasis of essential trace metals or affecting the numerous other metalloenzymes in the human proteome (Source: Nature Reviews Drug Discovery).

Other names

Cu/Zn metalloenzymesCopper-dependent enzymesZinc-dependent enzymesMetalloenzymesMetal-dependent proteins

Inhibition of enzymatic activity through coordination with the metal cofactor (Cu or Zn) or sequestration of the metal ion via chelation.