Molecular Basis of Substrate Recognition and Product Release by the Klebsiella pneumoniae Carbapenemase (KPC-2)

Carbapenem-resistant Enterobacteriaceae are resistant to most beta-lactain antibiotics due to the production of the Klebsiella pneumoniae carbapenemase (KPC-2) class A beta-lactamase. Here, we present the first product complex crystal structures of KPC-2 with beta-lactain antibiotics containing hydrolyzed cefotaxime and faropenerrr. They. rovide 'experimental insights into substrate-recognition by KPC-2 and its, unique eephalosporinase/carbapenemase activity. These structures also represent the first prodUct complexes for a wild type serine beta-lactamase, elucidating the product release mechanism of these enzymes in, general.