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Study Findings from Tokyo Institute of Technology Provide New Insights into Antibiotics

June 20, 2014

By a News Reporter-Staff News Editor at Drug Week -- Investigators publish new report on Drugs and Therapies. According to news reporting out of Kanagawa, Japan, by NewsRx editors, research stated, "Bacterial multidrug transporters AcrB and AcrD export -lactam antibiotics. Charged residues in the proximal binding pocket play a crucial role in -lactam selectivity."

Our news journalists obtained a quote from the research from the Tokyo Institute of Technology, "Proximal pocket acts as a substrate selection filter at the site of entry into the substrate translocation pathway. Our understanding of molecular mechanisms of antibiotic recognition is essential for overcoming drug resistance. -Lactams are mainstream antibiotics that are indicated for the prophylaxis and treatment of bacterial infections. The AcrA-AcrD-TolC multidrug efflux system confers much stronger resistance on Escherichia coli to clinically relevant anionic -lactam antibiotics than the homologous AcrA-AcrB-TolC system. Using an extensive combination of chimeric analysis and site-directed mutagenesis, we searched for residues that determine the difference in -lactam specificity between AcrB and AcrD. We identified three crucial residues at the proximal (or access) substrate binding pocket. The simultaneous replacement of these residues in AcrB by those in AcrD (Q569R, I626R, and E673G) transferred the -lactam specificity of AcrD to AcrB."

According to the news editors, the research concluded: "Our findings indicate for the first time that the difference in -lactam specificity between AcrB and AcrD relates to interactions of the antibiotic with residues in the proximal binding pocket."

For more information on this research see: beta-Lactam Selectivity of Multidrug Transporters AcrB and AcrD Resides in the Proximal Binding Pocket. Journal of Biological Chemistry, 2014;289(15):10680-10690. Journal of Biological Chemistry can be contacted at: Amer Soc Biochemistry Molecular Biology Inc, 9650 Rockville Pike, Bethesda, MD 20814-3996, USA. (American Society for Biochemistry and Molecular Biology -; Journal of Biological Chemistry -

Our news journalists report that additional information may be obtained by contacting N. Kobayashi, Tokyo Inst Technol, Dept. of Life Sci, Midori Ku, Yokohama, Kanagawa 2268501, Japan. Additional authors for this research include N. Tamura, H.W. van Veen, A. Yamaguchi and S. Murakami (see also Drugs and Therapies).

Keywords for this news article include: Asia, Antibacterial, Antibiotics, Antimicrobials, Japan, Kanagawa, beta-Lactams, Sulfur Compounds, Drugs and Therapies

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Source: Drug Week

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