Computational Redesign of the SHV-1 β-Lactamase/β-Lactamase Inhibitor Protein Interface

Structural and Computational Characterization of the SHV-1 -Lactamase- -Lactamase Inhibitor Protein Interface*

From the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093-0684, the Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106, the Biophysics Group and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, and **Research Service, Louis Stokes Veterans Affairs M...

Characterization of the inhibitor-resistant SHV β-lactamase SHV-107 in a clinical Klebsiella pneumoniae strain coproducing GES-7 enzyme.

The clinical Klebsiella pneumoniae INSRA6884 strain exhibited nonsusceptibility to all penicillins tested (MICs of 64 to >2,048 μg/ml). The MICs of penicillins were weakly reduced by clavulanate (from 2,048 to 512 μg/ml), and tazobactam restored piperacillin susceptibility. Molecular characterization identified the genes bla(GES-7) and a new β-lactamase gene, bla(SHV-107), which encoded an enzy...

Avibactam and inhibitor resistant SHV β - lactamases 1 2

Study of a Natural Mutant SHV-Type β-Lactamase, SHV-104, from Klebsiella pneumoniae

Klebsiella pneumoniae ML2011, a multiresistant isolate, was isolated from the Military Hospital of Tunis (Tunisia). The determination of the minimal inhibitory concentrations exhibited by K. pneumoniae ML2011 was performed by Etest. The crude extract of the isolates contains four different β -lactamases with pI 5.5, 7.3, 7.6, and 8.6. Only the β -lactamases with pI 7.3 and pI 8.6 were transferr...

Emergence of an inhibitor-resistant beta-lactamase (SHV-10) derived from an SHV-5 variant.

An inhibitor-resistant beta-lactamase (SHV-10), derived from an SHV-5 variant (SHV-9), was found in an Escherichia coli clinical isolate. In SHV-10, Ser-130 was replaced by Gly. The enzyme partially retained its ability to hydrolyze penicillins, but its activity against cephalosporins was drastically reduced. A Ser-130-->Gly mutant of the prototype SHV-5, obtained by site-directed mutagenesis, ...