L1 metallo-beta-lactamase (L1)

L1 metallo-beta-lactamase is a dizinc-dependent enzyme primarily produced by the opportunistic Gram-negative pathogen Stenotrophomonas maltophilia. As a member of the B3 subclass of metallo-beta-lactamases, it is distinguished by its unique tetrameric quaternary structure, which is essential for its catalytic activity. The enzyme facilitates broad-spectrum resistance to nearly all classes of beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, by catalyzing the hydrolysis of the beta-lactam ring. This resistance mechanism significantly complicates the treatment of healthcare-associated infections, particularly in immunocompromised individuals. While L1 is a major therapeutic target, it remains a challenge for drug development as it is not effectively inhibited by currently available clinical beta-lactamase inhibitors, necessitating the search for novel small-molecule or peptide-based inhibitors.

Other names

Metallo-beta-lactamase L1B3 metallo-beta-lactamaseL1 carbapenemaseblaL1 gene product

Inhibitors typically act through zinc chelation or competitive binding at the active site to prevent the hydrolysis of the beta-lactam ring.