5w3u: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of SsoPox AsB5 mutant (V27A-I76T-Y97W-Y99F-L130P-L226V)== | ==Crystal structure of SsoPox AsB5 mutant (V27A-I76T-Y97W-Y99F-L130P-L226V)== | ||
<StructureSection load='5w3u' size='340' side='right' caption='[[5w3u]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='5w3u' size='340' side='right'caption='[[5w3u]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5w3u]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W3U FirstGlance]. <br> | <table><tr><td colspan='2'>[[5w3u]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_35091 Atcc 35091]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W3U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W3U FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=GOL:GLYCEROL'>GOL</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=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='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> | ||
| Line 21: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 5w3u" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5w3u" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Phosphotriesterase|Phosphotriesterase]] | |||
*[[Serum Paraoxonase|Serum Paraoxonase]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 26: | Line 30: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aryldialkylphosphatase]] | [[Category: Aryldialkylphosphatase]] | ||
[[Category: Atcc 35091]] | |||
[[Category: Large Structures]] | |||
[[Category: Bergonzi, C]] | [[Category: Bergonzi, C]] | ||
[[Category: Chabriere, E]] | [[Category: Chabriere, E]] | ||
Revision as of 19:58, 20 November 2019
Crystal structure of SsoPox AsB5 mutant (V27A-I76T-Y97W-Y99F-L130P-L226V)Crystal structure of SsoPox AsB5 mutant (V27A-I76T-Y97W-Y99F-L130P-L226V)
Structural highlights
Function[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.[1] Publication Abstract from PubMedThe 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||||||