1JJE

IMP-1 METALLO BETA-LACTAMASE FROM PSEUDOMONAS AERUGINOSA IN COMPLEX WITH A BIARYL SUCCINIC ACID INHIBITOR (11)

Summary for 1JJE

• Entry DOI: 10.2210/pdb1jje/pdb
• Related: 1JJT
• Descriptor: IMP-1 METALLO BETA-LACTAMASE, ZINC ION, ACETATE ION, ... (5 entities in total)
• Functional Keywords: metallo-beta-lactamase inhibitor, succinic acid inhibitor, imp-1 metallo-beta-lactamase, hydrolase
• Biological source: Pseudomonas aeruginosa
• Cellular location: Periplasm : P52699
• Total number of polymer chains: 2
• Total formula weight: 50265.24

Authors

Fitzgerald, P.M.D.,Sharma, N. (deposition date: 2001-07-04, release date: 2001-07-25, Last modification date: 2024-11-13)

Primary citation

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.
Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase.
J.Biol.Chem., 276:31913-31918, 2001

PubMed Abstract: 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.

PubMed: 11390410
DOI: 10.1074/jbc.M104742200

Experimental method

X-RAY DIFFRACTION (1.8 Å)