Bacterial metalloenzyme

Bacterial metalloenzymes are a diverse group of proteins that require metal ions, such as zinc, iron, or manganese, as essential cofactors for their catalytic activity [1]. These enzymes play critical roles in fundamental bacterial processes, including protein maturation via peptide deformylase (PDF), lipid A biosynthesis via LpxC, and DNA synthesis [2]. A clinically significant group within this class is the metallo-beta-lactamases (MBLs), which utilize zinc to hydrolyze a broad spectrum of beta-lactam antibiotics, thereby driving multi-drug resistance in pathogens like Klebsiella pneumoniae and Pseudomonas aeruginosa [3]. Because many of these enzymes are essential for bacterial survival or virulence, they are highly attractive targets for novel antibiotic development [4]. Drugs targeting these enzymes, such as Taniborbactam or various PDF inhibitors, typically function by coordinating with the active-site metal ion to block substrate processing [5]. However, a major challenge in drug design is achieving sufficient selectivity to avoid cross-reactivity with essential human metalloenzymes, such as matrix metalloproteinases (MMPs) or angiotensin-converting enzyme (ACE), which could lead to significant adverse effects [6].

Other names

Metallo-enzymesBacterial metal-dependent enzymesBacterial metalloenzymesMetal-dependent bacterial hydrolases

Inhibition of enzymatic activity through competitive binding at the metal-containing active site or sequestration of essential metal cofactors.