PMID: 8606154Apr 1, 1996Paper

Systematic mutagenesis of the active site omega loop of TEM-1 beta-lactamase

Journal of Bacteriology
J Petrosino, Timothy Palzkill

Abstract

Beta-Lactamase is a bacterial protein that provides resistance against beta-lactam antibiotics. TEM-1 beta-lactamase is the most prevalent plasmid-mediated beta-lactamase in gram-negative bacteria. Normally, this enzyme has high levels of hydrolytic activity for penicillins, but mutant beta-lactamases have evolved with activity toward a variety of beta-lactam antibiotics. It has been shown that active site substitutions are responsible for changes in the substrate specificity. Since mutant beta-lactamases pose a serious threat to antimicrobial therapy, the mechanisms by which mutations can alter the substrate specificity of TEM-1 beta-lactamase are of interest. Previously, screens of random libraries encompassing 31 of 55 active site amino acid positions enabled the identification of the residues responsible for maintaining the substrate specificity of TEM-1 beta-lactamase. In addition to substitutions found in clinical isolates, many other specificity-altering mutations were also identified. Interestingly, many nonspecific substitutions in the N-terminal half of the active site omega loop were found to increase ceftazidime hydrolytic activity and decrease ampicillin hydrolytic activity. To complete the active sight study, eigh...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Aug 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·J G Sutcliffe
May 15, 1991·The Biochemical Journal·R P AmblerS G Waley
Aug 1, 1989·Antimicrobial Agents and Chemotherapy·A PhilipponG Jacoby
Jan 1, 1987·Methods in Enzymology·T A KunkelR A Zakour
Jan 1, 1984·British Medical Bulletin·A A Medeiros
May 16, 1980·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·R P Ambler
Aug 1, 1995·Antimicrobial Agents and Chemotherapy·S B VakulenkoS A Lerner
Jun 1, 1995·Antimicrobial Agents and Chemotherapy·K BushA A Medeiros
Jan 1, 1995·The Journal of Antimicrobial Chemotherapy·S K Du BoisS G Amyes
Jun 15, 1995·The Biochemical Journal·M VanhoveJ M Frère

❮ Previous
Next ❯

Citations

Nov 9, 2006·Protein Engineering, Design & Selection : PEDS·Michelle M MeyerFrances H Arnold
Jun 27, 2019·Journal of Biomolecular Structure & Dynamics·Dmitrii ShcherbininAlexey Egorov
Oct 3, 1998·The Journal of Biological Chemistry·C Cantu, T Palzkill
Mar 21, 2003·Protein Engineering·Mariana Peimbert, Lorenzo Segovia
May 10, 2013·The Journal of Biological Chemistry·Krisztina M Papp-WallaceMichiyoshi Nukaga
Jun 27, 2018·Antimicrobial Agents and Chemotherapy·Fabrice CompainMichel Arthur
Dec 15, 2019·Biomolecules·Alexey EgorovAlexander Veselovsky
Jul 15, 1997·FEMS Microbiology Letters·R A BonomoD M Shlaes
Oct 10, 2001·Angewandte Chemie·Sean V. TaylorDonald Hilvert
Sep 20, 2008·The Journal of Biological Chemistry·Carole UrbachPatrice Soumillion
Jan 27, 1999·Nature Biotechnology·D LegendreJ Fastrez
Jun 7, 2012·Protein Engineering, Design & Selection : PEDS·Yakov KipnisDan S Tawfik
Oct 6, 2011·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Mariagrazia PerilliGianfranco Amicosante
Oct 7, 2016·Nature Communications·Kathryn M HartGregory R Bowman
Aug 15, 2001·Antimicrobial Agents and Chemotherapy·C ArpinC Quentin
Mar 23, 2011·Biochemistry. Biokhimii︠a︡·M Yu RubtsovaA M Egorov
Jun 5, 2019·Experimental Biology and Medicine·Ben A Shurina, Richard C Page
Nov 7, 2012·International Journal of Antimicrobial Agents·Herbert HächlerRoger Stephan
Apr 30, 2021·Scientific Reports·Pedro A G TizeiVitor B Pinheiro
Aug 1, 1997·Current Opinion in Structural Biology·P Kast, D Hilvert
Sep 25, 1998·Trends in Microbiology·J PetrosinoT Palzkill
Dec 12, 2001·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·M Gniadkowski

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.