Nature Structural Biology
3, 290 - 297 (1996)
doi:10.1038/nsb0396-290
A potent new mode of  -lactamase inhibition revealed by the 1.7 Å X-ray crystallographic structure of the TEM-1−BLIP complexNatalie C.J. Strynadka1, Susan E. Jensen2, Pedro M. Alzari3
& Michael N.G. James1
1MRC Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
2Department of Biological Sciences, University of Alberta, Edmonton Alberta, Canada T6G 2E9
3Immunologie Struct., Institute Pasteur, 25 Rue Du Dr. Roux, F75724, Paris, Cedex 15, France The structure of TEM-1  -lactamase complexed with the inhibitor BLIP has been determined at 1.7 Å resolution. The two tandemly repeated domains of BLIP form a polar, concave surface that docks onto a predominantly polar, convex protrusion on the enzyme. The ability of BLIP to adapt to a variety of class A -lactamases is most likely due to an observed flexibility between the two domains of the inhibitor and to an extensive layer of water molecules entrapped between the enzyme and inhibitor. A -hairpin loop from domain 1 of BLIP is inserted into the active site of the -lactamase. The carboxylate of Asp 49 forms hydrogen bonds to four conserved, catalytic residues in the -lactamase, thereby mimicking the position of the penicillin G carboxylate observed in the acyl−enzyme complex of TEM-1 with substrate. This -hairpin may serve as a template with which to create a new family of peptide-analogue -lactamase inhibitors.
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