View source for 9b2j


==Structure of the quorum quenching lactonase GcL I237M mutant==
<StructureSection load='9b2j' size='340' side='right'caption='[[9b2j]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9b2j]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Parageobacillus_caldoxylosilyticus Parageobacillus caldoxylosilyticus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9B2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B2J 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</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=9b2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b2j OCA], [https://pdbe.org/9b2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b2j RCSB], [https://www.ebi.ac.uk/pdbsum/9b2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b2j ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A023DFE8_9BACI A0A023DFE8_9BACI] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Several enzymes from the metallo-beta-lactamase-like family of lactonases (MLLs) degrade N-acyl L-homoserine lactones (AHLs). They play a role in a microbial communication system known as quorum sensing, which contributes to pathogenicity and biofilm formation. Designing quorum quenching (QQ) enzymes that can interfere with this communication allows them to be used in a range of industrial and biomedical applications. However, tailoring these enzymes for specific communication signals requires a thorough understanding of their mechanisms and the physicochemical properties that determine their substrate specificities. We present here a detailed biochemical, computational, and structural study of GcL, which is a highly proficient and thermostable MLL with broad substrate specificity. We show that GcL not only accepts a broad range of substrates but also hydrolyzes these substrates through at least two different mechanisms. Further, the preferred mechanism appears to depend on both the substrate structure and/or the nature of the residues lining the active site. We demonstrate that other lactonases, such as AiiA and AaL, show similar mechanistic promiscuity, suggesting that this is a shared feature among MLLs. Mechanistic promiscuity has been seen previously in the lactonase/paraoxonase PON1, as well as with protein tyrosine phosphatases that operate via a dual general acid mechanism. The apparent prevalence of this phenomenon is significant from both a biochemical and protein engineering perspective: in addition to optimizing for specific substrates, it may be possible to optimize for specific mechanisms, opening new doors not just for the design of novel quorum quenching enzymes but also of other mechanistically promiscuous enzymes.

Catalytic Redundancies and Conformational Plasticity Drives Selectivity and Promiscuity in Quorum Quenching Lactonases.,Corbella M, Bravo J, Demkiv AO, Calixto AR, Sompiyachoke K, Bergonzi C, Brownless AR, Elias MH, Kamerlin SCL JACS Au. 2024 Aug 23;4(9):3519-3536. doi: 10.1021/jacsau.4c00404. eCollection , 2024 Sep 23. PMID:39328773<ref>PMID:39328773</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9b2j" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Parageobacillus caldoxylosilyticus]]
[[Category: Bergonzi C]]
[[Category: Bravo JA]]
[[Category: Calixto AR]]
[[Category: Corbella M]]
[[Category: Demkiv AO]]
[[Category: Elias M]]
[[Category: Kamerlin SCL]]
[[Category: Sompiyachoke K]]