X-RAY STRUCTURES AND MECHANISMS OF METALLO-beta-LACTAMASES

The metallo--lactamase superfamily comprises a remarkable set of enzymes that catalyse the hydrolysis of a wide range of substrates such as peptides, nucleic acids, antibiotics of the penicillin family and organophosphorus derivatives. In the past ten years, X-Ray structures of representative enzymes from different families have been determined, with the metallo--lactamases being the most represented. The salient common structural feature is the presence of a catalytic metal centre embedded within a  fold. The wealth of sequence and structural information on metallo--lactamases has allowed their classification into three subclasses. Structural information is now available for members of each subclass. Interestingly, these structures show the presence of either a mono or a di-nuclear metal centre in the active sites raising questions on the metal to protein stoichiometry under physiological conditions. In addition, the structures reveal a wide variability in the shape of the active site, which involves three variable loops lining the metal centre. For each enzyme a clear correlation is found between active site shape and substrate specificity.