View source for 5yxi


==Designed protein dRafX6==
<StructureSection load='5yxi' size='340' side='right'caption='[[5yxi]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yxi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YXI FirstGlance]. <br>
</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=5yxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yxi OCA], [https://pdbe.org/5yxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yxi RCSB], [https://www.ebi.ac.uk/pdbsum/5yxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yxi ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
To acquire extremely thermostable proteins of given functions is challenging for conventional protein engineering. Here we applied ABACUS, a statistical energy function we developed for de novo amino acid sequence design, to globally redesign a Ras-binding domain (RBD), and obtained an extremely thermostable RBD that unfolds reversibly at above 110 degrees C, the redesigned RBD experimentally confirmed to have expected structure and Ras-binding interface. Directed evolution of the redesigned RBD improved its Ras-binding affinity to the native protein level without excessive loss of thermostability. The designed amino acid substitutions were mostly at the protein surface. For many substitutions, strong epistasis or significantly differentiated effects on thermostability in the native sequence context relative to the redesigned sequence context were observed, suggesting the globally redesigned sequence to be unreachable through combining beneficial mutations of the native sequence. Further analyses revealed that by replacing 38 of a total of 48 non-interfacial surface residues at once, ABACUS redesign was able to globally "invert" the protein's charge distribution pattern in an optimized way. Our study demonstrates that computational protein design provides powerful new tools to solve challenging protein engineering problems.

De novo sequence redesign of a functional Ras-binding domain globally inverted the surface charge distribution and led to extreme thermostability.,Liu R, Wang J, Xiong P, Chen Q, Liu H Biotechnol Bioeng. 2021 May;118(5):2031-2042. doi: 10.1002/bit.27716. Epub 2021, Mar 1. PMID:33590881<ref>PMID:33590881</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5yxi" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Liu R]]