7aye: Difference between revisions
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==Crystal structure of the computationally designed chemically disruptable heterodimer LD6-MDM2== | |||
<StructureSection load='7aye' size='340' side='right'caption='[[7aye]], [[Resolution|resolution]] 2.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7aye]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Shigella_dysenteriae_Sd197 Shigella dysenteriae Sd197]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AYE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AYE 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]] 2.95Å</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=7aye FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aye OCA], [https://pdbe.org/7aye PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aye RCSB], [https://www.ebi.ac.uk/pdbsum/7aye PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aye ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Small-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules. To design ON-switches, we converted the CDHs into a multi-domain architecture which we refer to as activation by inhibitor release switches (AIR) that incorporate a rationally designed drug-insensitive receptor protein. CDHs and AIRs showed excellent performance as drug responsive switches to control combinations of synthetic circuits in mammalian cells. This approach effectively expands the chemical space and logic responses in living cells and provides a blueprint to develop new ON- and OFF-switches. | |||
A rational blueprint for the design of chemically-controlled protein switches.,Shui S, Gainza P, Scheller L, Yang C, Kurumida Y, Rosset S, Georgeon S, Di Roberto RB, Castellanos-Rueda R, Reddy ST, Correia BE Nat Commun. 2021 Oct 1;12(1):5754. doi: 10.1038/s41467-021-25735-9. PMID:34599176<ref>PMID:34599176</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7aye" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[MDM2 3D structures|MDM2 3D structures]] | |||
*[[Thiol:disulfide interchange protein 3D structures|Thiol:disulfide interchange protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Shigella dysenteriae Sd197]] | |||
[[Category: Correia BE]] | |||
[[Category: Lau K]] | |||
[[Category: Pojer F]] | |||
[[Category: Yang C]] | |||
Latest revision as of 11:35, 17 October 2024
Crystal structure of the computationally designed chemically disruptable heterodimer LD6-MDM2Crystal structure of the computationally designed chemically disruptable heterodimer LD6-MDM2
Structural highlights
Publication Abstract from PubMedSmall-molecule responsive protein switches are crucial components to control synthetic cellular activities. However, the repertoire of small-molecule protein switches is insufficient for many applications, including those in the translational spaces, where properties such as safety, immunogenicity, drug half-life, and drug side-effects are critical. Here, we present a computational protein design strategy to repurpose drug-inhibited protein-protein interactions as OFF- and ON-switches. The designed binders and drug-receptors form chemically-disruptable heterodimers (CDH) which dissociate in the presence of small molecules. To design ON-switches, we converted the CDHs into a multi-domain architecture which we refer to as activation by inhibitor release switches (AIR) that incorporate a rationally designed drug-insensitive receptor protein. CDHs and AIRs showed excellent performance as drug responsive switches to control combinations of synthetic circuits in mammalian cells. This approach effectively expands the chemical space and logic responses in living cells and provides a blueprint to develop new ON- and OFF-switches. A rational blueprint for the design of chemically-controlled protein switches.,Shui S, Gainza P, Scheller L, Yang C, Kurumida Y, Rosset S, Georgeon S, Di Roberto RB, Castellanos-Rueda R, Reddy ST, Correia BE Nat Commun. 2021 Oct 1;12(1):5754. doi: 10.1038/s41467-021-25735-9. PMID:34599176[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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