Identification and lead-in characterization of novel B3 metallo-β-lactamases

Metallo-beta-lactamases (MBLs) are zinc ion dependent enzymes that are responsible for the emergence and spread of beta-lactam resistance among bacterial pathogens. There are uncharacterized putative MBLs in the environment and their emergence is major interference in the generation of universal MBL inhibitors so it is important to identify and characterize novel MBLs. In this study two novel MBLs from Luteimonas sp. J29 and Pseudoxanthomonas mexicana were identified using B3 MBLs as query in BLAST database search. 3D models of putative MBLs generated by SWISS MODEL server taking AIM-1 as a structural template were verified using web based structure assessment and validation programs. Multiple sequence alignment revealed that residues important for substrate binding were conserved and loop region residues (156-162 and 223-230) important for catalysis are variable in these novel MBLs. Homology models showed typical MBL alpha/beta/beta/alpha sandwich fold containing six alpha helices, twelve beta strands and metal interacting residues are conserved in similar way as with other B3 MBLs. We report promising putative B3 MBLs with some variations and substrate docking studies revealed that novel MBLs have attributes close to acquired B3 MBLs.