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| {{STRUCTURE_1bue| PDB=1bue | SCENE= }} | | {{STRUCTURE_1bue| PDB=1bue | SCENE= }} |
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| '''NMC-A CARBAPENEMASE FROM ENTEROBACTER CLOACAE'''
| | ===NMC-A CARBAPENEMASE FROM ENTEROBACTER CLOACAE=== |
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| ==Overview==
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| The treatment of infectious diseases by penicillin and cephalosporin antibiotics is continuously challenged by the emergence and the dissemination of the numerous TEM and SHV mutant beta-lactamases with extended substrate profiles. These class A beta-lactamases nevertheless remain inefficient against carbapenems, the most effective antibiotics against clinically relevant pathogens. A new member of this enzyme class, NMC-A, was recently reported to hydrolyze at high rates, and hence destroy, all known beta-lactam antibiotics, including carbapenems and cephamycins. The crystal structure of NMC-A was solved to 1.64-A resolution, and reveals modifications in the topology of the substrate-binding site. While preserving the geometry of the essential catalytic residues, the active site of the enzyme presents a disulfide bridge between residues 69 and 238, and certain other structural differences compared with the other beta-lactamases. These unusual features in class A beta-lactamases involve amino acids that participate in enzyme-substrate interactions, which suggested that these structural factors should be related to the very broad substrate specificity of this enzyme. The comparison of the NMC-A structure with those of other class A enzymes and enzyme-ligand complexes, indicated that the position of Asn-132 in NMC-A provides critical additional space in the region of the protein where the poorer substrates for class A beta-lactamases, such as cephamycins and carbapenems, need to be accommodated. | | The line below this paragraph, {{ABSTRACT_PUBMED_9756914}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 9756914 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_9756914}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Class a carbapenemase]] | | [[Category: Class a carbapenemase]] |
| [[Category: Hydrolase]] | | [[Category: Hydrolase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:58:03 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 19:44:18 2008'' |