Structural Insights into Recognition of Hydrolyzed Carbapenems and Inhibitors by Subclass B3 Metallo-β-Lactamase SMB-1.

ABSTRACT: Metallo-β-lactamases (MBLs) confer resistance to carbapenems, and their increasing global prevalence is a growing clinical concern. To elucidate the mechanisms by which these enzymes recognize and hydrolyze carbapenems, we solved 1.4 to 1.6 Å crystal structures of SMB-1 (Serratia metallo-β-lactamase 1), a subclass B3 MBL, bound to hydrolyzed carbapenems (doripenem, meropenem, and imipenem). In these structures, SMB-1 interacts mainly with the carbapenem core structure via elements in the active site, including a zinc ion (Zn-2), Q157[113] (where the position in the SMB-1 sequence is in brackets after the BBL number), S221[175], and T223[177]. There is less contact with the carbapenem R2 side chains, strongly indicating that SMB-1 primarily recognizes the carbapenem core structure. This is

SUBMITTER: Wachino J 

PROVIDER: S-EPMC4914674 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature