View source for 7lno


==Structure of apo-CDD-1 beta-lactamase in imidazole and MPD==
<StructureSection load='7lno' size='340' side='right'caption='[[7lno]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7lno]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridioides_difficile Clostridioides difficile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LNO 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]] 1.58&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=7lno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lno OCA], [https://pdbe.org/7lno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lno RCSB], [https://www.ebi.ac.uk/pdbsum/7lno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lno ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A160YKM3_CLODI A0A160YKM3_CLODI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Class D beta-lactamases have risen to notoriety due to their wide spread in bacterial pathogens, propensity to inactivate clinically important beta-lactam antibiotics, and ability to withstand inhibition by the majority of classical beta-lactamase inhibitors. Understanding the catalytic mechanism of these enzymes is thus vitally important for the development of novel antibiotics and inhibitors active against infections caused by antibiotic-resistant bacteria. Here we report an in crystallo time-resolved study of the interaction of the class D beta-lactamase CDD-1 from Clostridioides difficile with the diazobicyclooctane inhibitor, avibactam. We show that the catalytic carboxylated lysine, a residue that is essential for both acylation and deacylation of beta-lactams, is sequestered within an internal sealed pocket of the enzyme. Time-resolved snapshots generated in this study allowed us to observe decarboxylation of the lysine and movement of CO2 and water molecules through a transient channel formed between the lysine pocket and the substrate binding site facilitated by rotation of the side chain of a conserved leucine residue. These studies provide novel insights on avibactam binding to CDD-1 and into the catalytic mechanism of class D beta-lactamases in general.

In Crystallo Time-Resolved Interaction of the Clostridioides difficile CDD-1 enzyme with Avibactam Provides New Insights into the Catalytic Mechanism of Class D beta-lactamases.,Stewart NK, Toth M, Stasyuk A, Vakulenko SB, Smith CA ACS Infect Dis. 2021 Apr 28. doi: 10.1021/acsinfecdis.1c00094. PMID:33908775<ref>PMID:33908775</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7lno" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridioides difficile]]
[[Category: Large Structures]]
[[Category: Smith CA]]
[[Category: Stewart NK]]
[[Category: Vakulenko SB]]