Structure of Apo- and Monometalated Forms of NDM-1?A Highly Potent Carbapenem-Hydrolyzing Metallo-?-Lactamase.
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| Format: | eBook |
| Language: | English |
| Published: |
Washington, D.C. : Oak Ridge, Tenn. :
United States. Department of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Department of Energy,
2011.
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| Abstract: | The New Delhi Metallo-b-lactamase (NDM-1) gene makes multiple pathogenic microorganisms resistant to all known blactam antibiotics. The rapid emergence of NDM-1 has been linked to mobile plasmids that move between different strains resulting in world-wide dissemination. Biochemical studies revealed that NDM-1 is capable of efficiently hydrolyzing a wide range of b-lactams, including many carbapenems considered as ??last resort?? antibiotics. The crystal structures of metal-free apo- and monozinc forms of NDM-1 presented here revealed an enlarged and flexible active site of class B1 metallo-blactamase. This site is capable of accommodating many b-lactam substrates by having many of the catalytic residues on flexible loops, which explains the observed extended spectrum activity of this zinc dependent b-lactamase. Indeed, five loops contribute ??keg?? residues in the active site including side chains involved in metal binding. Loop 1 in particular, shows conformational flexibility, apparently related to the acceptance and positioning of substrates for cleavage by a zinc-activated water molecule. |
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| Item Description: | Published through Scitech Connect. 09/08/2011. "Journal ID: ISSN 1932-6203." Kim, Youngchang ; Tesar, Christine ; Mire, Joseph ; Jedrzejczak, Robert ; Binkowski, Andrew ; Babnigg, Gyorgy ; Sacchettini, James ; Joachimiak, Andrzej ; |
| Physical Description: | Size: Article No. e24621 : digital, PDF file. |