Bacterial metalloenzymes and zinc-dependent proteins

Bacterial metalloenzymes and zinc-dependent proteins represent a diverse and essential class of enzymes that utilize metal ions, primarily zinc (Zn2+), as catalytic or structural cofactors. This broad category includes critical therapeutic targets such as metallo-beta-lactamases (MBLs), which degrade carbapenem antibiotics; LpxC (UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase), which is essential for lipid A biosynthesis in Gram-negative bacteria; and peptide deformylase (PDF), which is required for N-terminal protein processing. These enzymes are vital for bacterial survival, membrane integrity, and the evasion of host immune responses, making them high-priority candidates for the development of novel antibacterial agents. Drugs targeting these proteins typically function by binding to the zinc-coordinated active site to inhibit enzymatic activity. However, drug development is often complicated by the need for high selectivity to avoid inhibiting human zinc-dependent enzymes, such as matrix metalloproteinases, which could lead to significant off-target toxicity.

Other names

Bacterial zinc-dependent enzymesBacterial metalloproteinsZinc-dependent bacterial hydrolasesBacterial zinc metalloenzymes

Inhibition of enzymatic activity through coordination with the catalytic zinc ion in the active site, often utilizing zinc-binding pharmacophores like hydroxamates or boronic acids to block substrate binding or transition state formation.