The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA

Abstract

The Aeromonas hydrophila AE036 chromosome contains a cphA gene encoding a metallo-beta-lactamase which is highly active against carbapenem antibiotics such as imipenem. Here we show that the cphA gene product shares inhibitory similarities with a mammalian zinc peptidase, membrane dipeptidase (MDP; dehydropeptidase I). Both enzymes are able to hydrolyze imipenem and are inhibited by cilastatin. The active site similarities of these enzymes are not reflected in any significant primary sequence similarity.