4e3t: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Round 18 Arylesterase Variant of Phosphotriesterase with Bound Transition State Analog== | ==Round 18 Arylesterase Variant of Phosphotriesterase with Bound Transition State Analog== | ||
<StructureSection load='4e3t' size='340' side='right' caption='[[4e3t]], [[Resolution|resolution]] 1.65Å' scene=''> | <StructureSection load='4e3t' size='340' side='right' caption='[[4e3t]], [[Resolution|resolution]] 1.65Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4e3t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4e3t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aj_2067 Aj 2067]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E3T FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HLN:HEXYL(NAPHTHALEN-2-YLOXY)PHOSPHINIC+ACID'>HLN</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"><scene name='pdbligand=HLN:HEXYL(NAPHTHALEN-2-YLOXY)PHOSPHINIC+ACID'>HLN</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='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=4e3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e3t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e3t RCSB], [http://www.ebi.ac.uk/pdbsum/4e3t 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=4e3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e3t OCA], [http://pdbe.org/4e3t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e3t RCSB], [http://www.ebi.ac.uk/pdbsum/4e3t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e3t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 15: | Line 16: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4e3t" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
| Line 22: | Line 24: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aj 2067]] | |||
[[Category: Aryldialkylphosphatase]] | [[Category: Aryldialkylphosphatase]] | ||
[[Category: Jackson, C J]] | [[Category: Jackson, C J]] | ||
[[Category: Tawfik, D S]] | [[Category: Tawfik, D S]] | ||
Revision as of 05:41, 11 December 2016
Round 18 Arylesterase Variant of Phosphotriesterase with Bound Transition State AnalogRound 18 Arylesterase Variant of Phosphotriesterase with Bound Transition State Analog
Structural highlights
Publication Abstract from PubMedOptimization 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 AlsoReferences
|
| ||||||||||||||||||