PMID: 11343789May 10, 2001Paper

Mutagenesis of amino acid residues in the SHV-1 beta-lactamase: the premier role of Gly238Ser in penicillin and cephalosporin resistance

Biochimica Et Biophysica Acta
Andrea M HujerRobert A Bonomo

Abstract

The recent availability of the SHV-1 beta-lactamase crystal structure provides a framework for the understanding of the functional role of amino acid residues in this enzyme. To that end, we have constructed by site-directed mutagenesis 18 variants of the SHV beta-lactamase: an extended spectrum group: Gly238Ser, Gly238Ser-Glu240Lys, Asp104Lys-Gly238Ser, Asp104Lys-Thr235Ser-Gly238Ser, Asp179Asn, Arg164His, and Arg164Ser; an inhibitor resistant group: Arg244Ser, Met69Ile, Met69Leu, and Ser130Gly; mutants that are synergistic with those that confer resistance to oxyimino-cephalosporins: Asp104Glu, Asp104Lys, Glu240Lys, and Glu240Gln; and structurally conserved mutants: Thr235Ser, Thr235Ala and Glu166Ala. Among the extended spectrum group the combination of high-level ampicillin and cephalosporin resistance was demonstrated in the Escherichia coli DH10B strains possessing the Gly238Ser mutation: Gly238Ser, Gly238Ser-Glu240Lys, Asp104Lys-Gly238Ser, and Asp104Lys-Thr235Ser-Gly238Ser. Of the inhibitor resistant group, the Ser130Gly mutant was the most resistant to ampicillin/clavulanate. Using a polyclonal anti-SHV antibody, we assayed steady state protein expression levels of the SHV beta-lactamase variants. Mutants with the Gly238S...Continue Reading

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Citations

Oct 29, 2008·The Journal of Biological Chemistry·Priyaranjan PattanaikRobert A Bonomo
May 11, 2011·Antimicrobial Agents and Chemotherapy·Christopher R BethelRobert A Bonomo
Jan 21, 2010·Antimicrobial Agents and Chemotherapy·Sarah M DrawzRobert A Bonomo
Sep 20, 2006·Antimicrobial Agents and Chemotherapy·Christopher R BethelRobert A Bonomo
Mar 2, 2011·Antimicrobial Agents and Chemotherapy·Jared M SampsonFocco van den Akker
Jun 19, 2008·Antimicrobial Agents and Chemotherapy·Christopher R BethelRobert A Bonomo
Sep 25, 2004·Antimicrobial Agents and Chemotherapy·Andrea M HujerRobert A Bonomo
Jun 25, 2004·Antimicrobial Agents and Chemotherapy·S HaeggmanS Brisse
Jan 13, 2010·Clinical Microbiology Reviews·Sarah M Drawz, Robert A Bonomo
Sep 9, 2008·Journal of Molecular Biology·Kimberly A ReynoldsTracy M Handel
Jun 24, 2015·Journal of Medicinal Chemistry·Emilia CaselliFabio Prati
Jun 6, 2014·Biochemistry·Hossein Heidari TorkabadiPaul R Carey
Oct 2, 2002·The Journal of Biological Chemistry·Marion S HelfandRobert A Bonomo
Apr 15, 2020·Antimicrobial Agents and Chemotherapy·Svetlana NeubauerOliwia Makarewicz
Jul 1, 2006·The Journal of Biological Chemistry·Kimberly A ReynoldsTracy M Handel
Sep 3, 2008·Journal of the American Chemical Society·Michiyosi NukagaRobert A Bonomo
Aug 28, 2002·International Journal of Medical Microbiology : IJMM·Fahd K MajiduddinTimothy G Palzkill

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