Standardized Residue Numbering and Secondary Structure Nomenclature in the Class D β‑Lactamases

Over 1370 class D β-lactamases are currently known,
and they
pose a serious threat to the effective treatment of many infectious
diseases, particularly in some pathogenic bacteria where evolving
carbapenemase activity has been reported. Detailed understanding of
their molecular biology, enzymology, and structural biology are critically
important, but the lack of a standardized residue numbering scheme
and inconsistent secondary structure annotation has made comparative
analyses sometimes difficult and cumbersome. Compounding this, in
the post-AlphaFold world where we currently find ourselves, an extraordinary
wealth of detailed structural information on these enzymes is literally
at our fingertips; therefore it is vitally important that a standard
numbering system is in place to facilitate the accurate and straightforward
analysis of their structures. Here we present a residue numbering
and secondary structure scheme for the class D enzymes based on the
sequence and structure of OXA-48 and apply it to test targets to demonstrate
the ease with which it can be used.