1bue: Difference between revisions

[[Image:1bue.jpg|left|200px]]<br /><applet load="1bue" size="350" color="white" frame="true" align="right" spinBox="true"  

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.

1BUE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterobacter_cloacae Enterobacter cloacae]. Active as [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BUE OCA].  

[[Category: Frere, J M.]]

[[Category: Pedelacq, J D.]]

[[Category: Samama, J P.]]

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