View source for 4hbt


==Crystal structure of native CTX-M-15 extended-spectrum beta-lactamase==
<StructureSection load='4hbt' size='340' side='right'caption='[[4hbt]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hbt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HBT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hbt OCA], [https://pdbe.org/4hbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hbt RCSB], [https://www.ebi.ac.uk/pdbsum/4hbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hbt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q9EXV5_ECOLX Q9EXV5_ECOLX] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Although beta-lactams have been the most effective class of antibacterial agents used in clinical practice for the past half century, their effectiveness on Gram-negative bacteria has been eroded due to the emergence and spread of beta-lactamase enzymes that are not affected by currently marketed beta-lactam/beta-lactamase inhibitor combinations. Avibactam is a novel, covalent, non-beta-lactam beta-lactamase inhibitor presently in clinical development in combination with either ceftaroline or ceftazidime. In vitro studies show that avibactam may restore the broad-spectrum activity of cephalosporins against class A, class C and some class D beta-lactamases. Here we describe the structure of two clinically important beta-lactamase enzymes bound to avibactam, the class A CTX-M-15 extended-spectrum beta-lactamase and class C Pseudomonas aeruginosa AmpC beta-lactamase, which together provide insight into the binding modes for the respective enzyme classes. The structure reveals a similar binding mode in both enzymes and thus provides a rationale for the broad-spectrum inhibitory activity of avibactam. Identification of the key residues surrounding the binding pocket allows for a better understanding of the potency of this scaffold. Finally, avibactam has recently been shown to be a reversible inhibitor and the structure provides insights into the mechanism of avibactam recyclization. Analysis of the ultra-high resolution CTX-M-15 structure suggests how the deacylation mechanism favors recyclization over hydrolysis.

Structural Insight into Potent Broad-spectrum Inhibition with Reversible Recyclization Mechanism: Avibactam in Complex with CTX-M-15 and Pseudomonas aeruginosa AmpC beta-lactamases.,Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD Antimicrob Agents Chemother. 2013 Feb 25. PMID:23439634<ref>PMID:23439634</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hbt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Benvenuti M]]
[[Category: Black MT]]
[[Category: Bruneau JM]]
[[Category: Docquier JD]]
[[Category: Mangani S]]
[[Category: Miossec C]]
[[Category: Rossolini GM]]