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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase.

IMP-1 metallo-beta-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes beta-lactam antibiotics, including carbapenems, rendering them ineffective. Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility. We have identified a series of 2,3-(S,S)-disubstituted succinic acids that are potent inhibitors of IMP-1. Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors.[1]


  1. Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase. Toney, J.H., Hammond, G.G., Fitzgerald, P.M., Sharma, N., Balkovec, J.M., Rouen, G.P., Olson, S.H., Hammond, M.L., Greenlee, M.L., Gao, Y.D. J. Biol. Chem. (2001) [Pubmed]
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