Strategies to Name Metallo-β-Lactamases and Number Their Amino Acid Residues

Abstract

Metallo-β-lactamases (MBLs), also known as class B β-lactamases (BBLs), are Zn(II)-containing enzymes able to inactivate a broad range of β-lactams, the most commonly used antibiotics, including life-saving carbapenems. They have been known for about six decades, yet they have only gained much attention as a clinical problem for about three decades. The naming conventions of these enzymes have changed over time and followed various strategies, sometimes leading to confusion. We are summarizing the naming strategies of the currently known MBLs. These enzymes are quite diverse on the amino acid sequence level but structurally similar. Problems trying to describe conserved residues, such as Zn(II) ligands and other catalytically important residues, which have different numbers in different sequences, have led to the establishment of a standard numbering scheme for BBLs. While well intended, the standard numbering scheme is not trivial and has not been applied consistently. We revisit this standard numbering scheme and suggest some strategies for how its implementation could be made more accessible to researchers. Standard numbering facilitates the comparison of different enzymes as well as their interaction with novel antibiotics and BBL inhibitors.