6zwb: Difference between revisions
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==== | ==Z-SBTub3 photoswitch bound to tubulin-DARPin D1 complex== | ||
<StructureSection load='6zwb' size='340' side='right'caption='[[6zwb]]' scene=''> | <StructureSection load='6zwb' size='340' side='right'caption='[[6zwb]], [[Resolution|resolution]] 1.75Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6zwb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZWB FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.747Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=QRN:5-[2-(1,3-benzothiazol-2-yl)ethyl]-2-methoxy-phenol'>QRN</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=6zwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zwb OCA], [https://pdbe.org/6zwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zwb RCSB], [https://www.ebi.ac.uk/pdbsum/6zwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zwb ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/TBA1B_BOVIN TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Optically controlled chemical reagents, termed "photopharmaceuticals," are powerful tools for precise spatiotemporal control of proteins particularly when genetic methods, such as knockouts or optogenetics are not viable options. However, current photopharmaceutical scaffolds, such as azobenzenes are intolerant of GFP/YFP imaging and are metabolically labile, posing severe limitations for biological use. We rationally designed a photoswitchable "SBT" scaffold to overcome these problems, then derivatized it to create exceptionally metabolically robust and fully GFP/YFP-orthogonal "SBTub" photopharmaceutical tubulin inhibitors. Lead compound SBTub3 allows temporally reversible, cell-precise, and even subcellularly precise photomodulation of microtubule dynamics, organization, and microtubule-dependent processes. By overcoming the previous limitations of microtubule photopharmaceuticals, SBTubs offer powerful applications in cell biology, and their robustness and druglikeness are favorable for intracellular biological control in in vivo applications. We furthermore expect that the robustness and imaging orthogonality of the SBT scaffold will inspire other derivatizations directed at extending the photocontrol of a range of other biological targets. | |||
A Robust, GFP-Orthogonal Photoswitchable Inhibitor Scaffold Extends Optical Control over the Microtubule Cytoskeleton.,Gao L, Meiring JCM, Kraus Y, Wranik M, Weinert T, Pritzl SD, Bingham R, Ntouliou E, Jansen KI, Olieric N, Standfuss J, Kapitein LC, Lohmuller T, Ahlfeld J, Akhmanova A, Steinmetz MO, Thorn-Seshold O Cell Chem Biol. 2021 Feb 18;28(2):228-241.e6. doi: , 10.1016/j.chembiol.2020.11.007. Epub 2020 Dec 3. PMID:33275880<ref>PMID:33275880</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6zwb" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Tubulin 3D Structures|Tubulin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Bos taurus]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: Ahlfeld J]] | |||
[[Category: Bingham R]] | |||
[[Category: Gao L]] | |||
[[Category: Kraus YCM]] | |||
[[Category: Ntouliou E]] | |||
[[Category: Olieric N]] | |||
[[Category: Standfuss J]] | |||
[[Category: Steinmetz MO]] | |||
[[Category: Thorn-Seshold O]] | |||
[[Category: Weinert T]] | |||
[[Category: Wranik M]] | |||
Latest revision as of 14:59, 1 February 2024
Z-SBTub3 photoswitch bound to tubulin-DARPin D1 complexZ-SBTub3 photoswitch bound to tubulin-DARPin D1 complex
Structural highlights
FunctionTBA1B_BOVIN Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. Publication Abstract from PubMedOptically controlled chemical reagents, termed "photopharmaceuticals," are powerful tools for precise spatiotemporal control of proteins particularly when genetic methods, such as knockouts or optogenetics are not viable options. However, current photopharmaceutical scaffolds, such as azobenzenes are intolerant of GFP/YFP imaging and are metabolically labile, posing severe limitations for biological use. We rationally designed a photoswitchable "SBT" scaffold to overcome these problems, then derivatized it to create exceptionally metabolically robust and fully GFP/YFP-orthogonal "SBTub" photopharmaceutical tubulin inhibitors. Lead compound SBTub3 allows temporally reversible, cell-precise, and even subcellularly precise photomodulation of microtubule dynamics, organization, and microtubule-dependent processes. By overcoming the previous limitations of microtubule photopharmaceuticals, SBTubs offer powerful applications in cell biology, and their robustness and druglikeness are favorable for intracellular biological control in in vivo applications. We furthermore expect that the robustness and imaging orthogonality of the SBT scaffold will inspire other derivatizations directed at extending the photocontrol of a range of other biological targets. A Robust, GFP-Orthogonal Photoswitchable Inhibitor Scaffold Extends Optical Control over the Microtubule Cytoskeleton.,Gao L, Meiring JCM, Kraus Y, Wranik M, Weinert T, Pritzl SD, Bingham R, Ntouliou E, Jansen KI, Olieric N, Standfuss J, Kapitein LC, Lohmuller T, Ahlfeld J, Akhmanova A, Steinmetz MO, Thorn-Seshold O Cell Chem Biol. 2021 Feb 18;28(2):228-241.e6. doi: , 10.1016/j.chembiol.2020.11.007. Epub 2020 Dec 3. PMID:33275880[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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