4pcn: Difference between revisions
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==Phosphotriesterase variant R22== | |||
<StructureSection load='4pcn' size='340' side='right'caption='[[4pcn]], [[Resolution|resolution]] 1.54Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4pcn]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Brevundimonas_diminuta Brevundimonas diminuta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PCN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PCN FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.54Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4pcn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pcn OCA], [https://pdbe.org/4pcn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pcn RCSB], [https://www.ebi.ac.uk/pdbsum/4pcn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pcn ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A060GSW0_BREDI A0A060GSW0_BREDI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Enzymes must be ordered to allow the stabilization of transition states by their active sites, yet dynamic enough to adopt alternative conformations suited to other steps in their catalytic cycles. The biophysical principles that determine how specific protein dynamics evolve and how remote mutations affect catalytic activity are poorly understood. Here we examine a 'molecular fossil record' that was recently obtained during the laboratory evolution of a phosphotriesterase from Pseudomonas diminuta to an arylesterase. Analysis of the structures and dynamics of nine protein variants along this trajectory, and three rationally designed variants, reveals cycles of structural destabilization and repair, evolutionary pressure to 'freeze out' unproductive motions and sampling of distinct conformations with specific catalytic properties in bi-functional intermediates. This work establishes that changes to the conformational landscapes of proteins are an essential aspect of molecular evolution and that change in function can be achieved through enrichment of preexisting conformational sub-states. | |||
The role of protein dynamics in the evolution of new enzyme function.,Campbell E, Kaltenbach M, Correy GJ, Carr PD, Porebski BT, Livingstone EK, Afriat-Jurnou L, Buckle AM, Weik M, Hollfelder F, Tokuriki N, Jackson CJ Nat Chem Biol. 2016 Sep 12. doi: 10.1038/nchembio.2175. PMID:27618189<ref>PMID:27618189</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Campbell | <div class="pdbe-citations 4pcn" style="background-color:#fffaf0;"></div> | ||
[[Category: Jackson | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Phosphotriesterase 3D structures|Phosphotriesterase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Brevundimonas diminuta]] | |||
[[Category: Large Structures]] | |||
[[Category: Campbell E]] | |||
[[Category: Jackson CJ]] | |||
[[Category: Kaltenbach M]] | |||
[[Category: Tokuriki N]] | |||
Latest revision as of 10:15, 27 September 2023
Phosphotriesterase variant R22Phosphotriesterase variant R22
Structural highlights
FunctionPublication Abstract from PubMedEnzymes must be ordered to allow the stabilization of transition states by their active sites, yet dynamic enough to adopt alternative conformations suited to other steps in their catalytic cycles. The biophysical principles that determine how specific protein dynamics evolve and how remote mutations affect catalytic activity are poorly understood. Here we examine a 'molecular fossil record' that was recently obtained during the laboratory evolution of a phosphotriesterase from Pseudomonas diminuta to an arylesterase. Analysis of the structures and dynamics of nine protein variants along this trajectory, and three rationally designed variants, reveals cycles of structural destabilization and repair, evolutionary pressure to 'freeze out' unproductive motions and sampling of distinct conformations with specific catalytic properties in bi-functional intermediates. This work establishes that changes to the conformational landscapes of proteins are an essential aspect of molecular evolution and that change in function can be achieved through enrichment of preexisting conformational sub-states. The role of protein dynamics in the evolution of new enzyme function.,Campbell E, Kaltenbach M, Correy GJ, Carr PD, Porebski BT, Livingstone EK, Afriat-Jurnou L, Buckle AM, Weik M, Hollfelder F, Tokuriki N, Jackson CJ Nat Chem Biol. 2016 Sep 12. doi: 10.1038/nchembio.2175. PMID:27618189[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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