4gy1: Difference between revisions

Revision as of 08:28, 4 August 2016

Round 18 Arylesterase Variant of Phosphotriesterase with Bound Cacodylate

Structural highlights

4gy1 is a 2 chain structure with sequence from Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CAC, ZN
NonStd Res:	KCX
Related:	4e3t, 4gy0
Activity:	Aryldialkylphosphatase, with EC number 3.1.8.1
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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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OCA

[1] 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

[1]

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 ==Round 18 Arylesterase Variant of Phosphotriesterase with Bound Cacodylate==
 <StructureSection load='4gy1' size='340' side='right' caption='[[4gy1]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4gy1]] is a 2 chain structure with sequence from [http://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 [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 [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>
 </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>
 <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">[[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://www.rcsb.org/pdb/explore.do?structureId=4gy1 RCSB], [http://www.ebi.ac.uk/pdbsum/4gy1 PDBsum]</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>
 <div style="background-color:#fffaf0;">
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4gy1" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 25: / Line 27: @@
 </StructureSection>
 [[Category: Aryldialkylphosphatase]]
-[[Category: Synthetic construct]]
+[[Category: Synthetic construct sequences]]
 [[Category: Jackson, C J]]
 [[Category: Tawfik, D S]]

4gy1: Difference between revisions

Revision as of 08:28, 4 August 2016

Round 18 Arylesterase Variant of Phosphotriesterase with Bound Cacodylate

Structural highlights

Publication Abstract from PubMed

See Also

References

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