Metalloenzymes with dinuclear metal centers

Metalloenzymes with dinuclear metal centers represent a broad and functionally diverse class of enzymes that utilize two metal ions—such as zinc, iron, manganese, copper, or nickel—in close proximity within their active sites to facilitate complex chemical reactions. These metal centers work cooperatively to perform tasks that mononuclear centers cannot, such as the hydrolysis of highly stable phosphodiester bonds or the activation of molecular oxygen for redox signaling. Key examples include metallo-beta-lactamases (Zn-Zn), which are major drivers of antibiotic resistance, and HIV integrase (Mg-Mg/Mn-Mn), which is a primary target for antiretroviral therapy. In human health, dinuclear enzymes like arginase (Mn-Mn) and purple acid phosphatase (Fe-Zn/Fe-Fe) are involved in the urea cycle and bone resorption, respectively, making them significant targets for cancer and osteoporosis treatments. Therapeutic intervention typically involves small molecules with metal-binding pharmacophores (MBPs) that coordinate directly to the metal ions, though achieving high selectivity remains a major challenge due to the ubiquity of metal-dependent processes in the body.

Other names

Binuclear metalloenzymesBimetallic enzymesDinuclear metalloproteinsDi-metal enzymesBinuclear metallohydrolases

Inhibition of enzymatic activity through the coordination of metal-binding pharmacophores (MBPs) to the dinuclear metal center, typically bridging the two metal ions or displacing essential water molecules and substrates required for catalysis.