View source for 5vsa


==Crystal structure of SsoPox AsA1 mutant (C258L-I261F-W263A)==
<StructureSection load='5vsa' size='340' side='right'caption='[[5vsa]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5vsa]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_35091 Atcc 35091]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VSA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2vc5|2vc5]], [[2vc7|2vc7]], [[5vri|5vri]], [[5vrk|5vrk]], [[5w3u|5w3u]], [[5w3w|5w3w]], [[5w3z|5w3z]]</div></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aryldialkylphosphatase Aryldialkylphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.8.1 3.1.8.1] </span></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=5vsa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vsa OCA], [https://pdbe.org/5vsa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vsa RCSB], [https://www.ebi.ac.uk/pdbsum/5vsa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vsa ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/PHP_SULSO PHP_SULSO]] Has a low paraoxonase activity. Also active, but with a lower activity, against other oregano-phosphorus insecticides such as Dursban, Coumaphos, pNP-butanoate or parathion.<ref>PMID:15909078</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The redesign of enzyme active sites to alter their function or specificity is a difficult yet appealing challenge. Here we used a structure-based design approach to engineer the lactonase SsoPox from Sulfolobus solfataricus into a phosphotriesterase. The five best variants were characterized and their structure was solved. The most active variant, alphasD6 (V27A-Y97W-L228M-W263M) demonstrates a large increase in catalytic efficiencies over the wild-type enzyme, with increases of 2,210-fold, 163-fold, 58-fold, 16-fold against methyl-parathion, malathion, ethyl-paraoxon, and methyl-paraoxon, respectively. Interestingly, the best mutants are also capable of degrading fensulfothion, which is reported to be an inhibitor for the wild-type enzyme, as well as others that are not substrates of the starting template or previously reported W263 mutants. The broad specificity of these engineered variants makes them promising candidates for the bioremediation of organophosphorus compounds. Analysis of their structures reveals that the increase in activity mainly occurs through the destabilization of the active site loop involved in substrate binding, and it has been observed that the level of disorder correlates with the width of the enzyme specificity spectrum. This finding supports the idea that active site conformational flexibility is essential to the acquisition of broader substrate specificity.

Rational engineering of a native hyperthermostable lactonase into a broad spectrum phosphotriesterase.,Jacquet P, Hiblot J, Daude D, Bergonzi C, Gotthard G, Armstrong N, Chabriere E, Elias M Sci Rep. 2017 Dec 1;7(1):16745. doi: 10.1038/s41598-017-16841-0. PMID:29196634<ref>PMID:29196634</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5vsa" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphotriesterase 3D structures|Phosphotriesterase 3D structures]]
*[[Serum Paraoxonase|Serum Paraoxonase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aryldialkylphosphatase]]
[[Category: Atcc 35091]]
[[Category: Large Structures]]
[[Category: Bergonzi, C]]
[[Category: Chabriere, E]]
[[Category: Daude, D]]
[[Category: Elias, M]]
[[Category: Gotthard, G]]
[[Category: Hiblot, J]]
[[Category: Jacquet, P]]
[[Category: Hydrolase]]
[[Category: Insecticides]]
[[Category: Lactonase]]
[[Category: Mutant]]
[[Category: Organophosphate]]
[[Category: Organophosphorous]]
[[Category: Phosphotriesterase]]
[[Category: Quorum sensing]]