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

Abstract

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.