4xay: Difference between revisions
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<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=4xay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xay OCA], [http://pdbe.org/4xay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xay RCSB], [http://www.ebi.ac.uk/pdbsum/4xay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xay ProSAT]</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=4xay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xay OCA], [http://pdbe.org/4xay PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xay RCSB], [http://www.ebi.ac.uk/pdbsum/4xay PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xay ProSAT]</span></td></tr> | ||
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== 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> | |||
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<div class="pdbe-citations 4xay" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
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Revision as of 12:12, 3 October 2016
Cycles of destabilization and repair underlie evolutionary transitions in enzymesCycles of destabilization and repair underlie evolutionary transitions in enzymes
Structural highlights
Publication 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. References
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