The renal membrane dipeptidase (dehydropeptidase I) inhibitor, cilastatin, inhibits the bacterial metallo-beta-lactamase enzyme CphA.
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.
D000818:Animals; D001426:Bacterial Proteins; D015377:Cilastatin / Q000494:pharmacology*; D004150:Dipeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D006868:Hydrolysis; D015378:Imipenem / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000648:ultrastructure; D007700:Kinetics; D008566:Membranes / Q000201:enzymology; D013552:Swine; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D004151:Dipeptides; D065093:beta-Lactamase Inhibitors; D015377:Cilastatin; D015378:Imipenem; D004150:Dipeptidases; C038937:dipeptidase; D001618:beta-Lactamases