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| | <StructureSection load='5wc7' size='340' side='right'caption='[[5wc7]], [[Resolution|resolution]] 1.43Å' scene=''> | | <StructureSection load='5wc7' size='340' side='right'caption='[[5wc7]], [[Resolution|resolution]] 1.43Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wc7]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WC7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WC7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wc7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WC7 FirstGlance]. <br> |
| - | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.43Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5wc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc7 OCA], [http://pdbe.org/5wc7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wc7 RCSB], [http://www.ebi.ac.uk/pdbsum/5wc7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc7 ProSAT]</span></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=5wc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc7 OCA], [https://pdbe.org/5wc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wc7 RCSB], [https://www.ebi.ac.uk/pdbsum/5wc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. | + | [https://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptidylprolyl isomerase]]
| + | [[Category: Fraser JS]] |
| - | [[Category: Fraser, J S]] | + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Proline isomerase]]
| + | |
| Structural highlights
Function
PPIA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Publication Abstract from PubMed
Rational design and directed evolution have proved to be successful approaches to increase catalytic efficiencies of both natural and artificial enzymes. Protein dynamics is recognized as important, but due to the inherent flexibility of biological macromolecules it is often difficult to distinguish which conformational changes are directly related to function. Here, we use directed evolution on an impaired mutant of the proline isomerase CypA and identify two second-shell mutations that partially restore its catalytic activity. We show both kinetically, using NMR spectroscopy, and structurally, by room-temperature X-ray crystallography, how local perturbations propagate through a large allosteric network to facilitate conformational dynamics. The increased catalysis selected for in the evolutionary screen is correlated with an accelerated interconversion between the two catalytically essential conformational sub-states, which are both captured in the high-resolution X-ray ensembles. Our data provide a glimpse of an evolutionary trajectory and show how subtle changes can fine-tune enzyme function.
Rescue of conformational dynamics in enzyme catalysis by directed evolution.,Otten R, Liu L, Kenner LR, Clarkson MW, Mavor D, Tawfik DS, Kern D, Fraser JS Nat Commun. 2018 Apr 3;9(1):1314. doi: 10.1038/s41467-018-03562-9. PMID:29615624[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Otten R, Liu L, Kenner LR, Clarkson MW, Mavor D, Tawfik DS, Kern D, Fraser JS. Rescue of conformational dynamics in enzyme catalysis by directed evolution. Nat Commun. 2018 Apr 3;9(1):1314. doi: 10.1038/s41467-018-03562-9. PMID:29615624 doi:http://dx.doi.org/10.1038/s41467-018-03562-9
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