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| | <StructureSection load='4gy1' size='340' side='right'caption='[[4gy1]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='4gy1' size='340' side='right'caption='[[4gy1]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gy1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GY1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GY1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gy1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GY1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gy1 OCA], [https://pdbe.org/4gy1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gy1 RCSB], [https://www.ebi.ac.uk/pdbsum/4gy1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gy1 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4e3t|4e3t]], [[4gy0|4gy0]]</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aryldialkylphosphatase Aryldialkylphosphatase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4gy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gy1 OCA], [http://pdbe.org/4gy1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gy1 RCSB], [http://www.ebi.ac.uk/pdbsum/4gy1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gy1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/OPD_BREDI OPD_BREDI] Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Phosphotriesterase|Phosphotriesterase]] | + | *[[Phosphotriesterase 3D structures|Phosphotriesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aryldialkylphosphatase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Synthetic construct sequences]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Jackson, C J]] | + | [[Category: Jackson CJ]] |
| - | [[Category: Tawfik, D S]] | + | [[Category: Tawfik DS]] |
| - | [[Category: Tokuriki, N]] | + | [[Category: Tokuriki N]] |
| - | [[Category: Alpha/beta hydrolase]]
| + | |
| - | [[Category: Arylesterase]]
| + | |
| - | [[Category: Carboxylated lysine]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
OPD_BREDI Has an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates. All of the phosphate triesters found to be substrates are synthetic compounds. The identity of any naturally occurring substrate for the enzyme is unknown. Has no detectable activity with phosphate monoesters or diesters and no activity as an esterase or protease. It catalyzes the hydrolysis of the insecticide paraoxon at a rate approaching the diffusion limit and thus appears to be optimally evolved for utilizing this synthetic substrate.
Publication Abstract from PubMed
Optimization processes, such as evolution, are constrained by diminishing returns-the closer the optimum, the smaller the benefit per mutation, and by tradeoffs-improvement of one property at the cost of others. However, the magnitude and molecular basis of these parameters, and their effect on evolutionary transitions, remain unknown. Here we pursue a complete functional transition of an enzyme with a >10(9)-fold change in the enzyme's selectivity using laboratory evolution. We observed strong diminishing returns, with the initial mutations conferring >25-fold higher improvements than later ones, and asymmetric tradeoffs whereby the gain/loss ratio of the new/old activity decreased 400-fold from the beginning of the trajectory to its end. We describe the molecular basis for these phenomena and suggest they have an important role in shaping natural proteins. These findings also suggest that the catalytic efficiency and specificity of many natural enzymes may be far from their optimum.
Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme.,Tokuriki N, Jackson CJ, Afriat-Jurnou L, Wyganowski KT, Tang R, Tawfik DS Nat Commun. 2012 Dec 4;3:1257. doi: 10.1038/ncomms2246. PMID:23212386[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tokuriki N, Jackson CJ, Afriat-Jurnou L, Wyganowski KT, Tang R, Tawfik DS. Diminishing returns and tradeoffs constrain the laboratory optimization of an enzyme. Nat Commun. 2012 Dec 4;3:1257. doi: 10.1038/ncomms2246. PMID:23212386 doi:10.1038/ncomms2246
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