6ZWB

Z-SBTub3 photoswitch bound to tubulin-DARPin D1 complex

Summary for 6ZWB

• Entry DOI: 10.2210/pdb6zwb/pdb
• Descriptor: Tubulin alpha-1B chain, Tubulin beta-2B chain, Designed Ankyrin Repeat Protein (DARPIN) D1, ... (8 entities in total)
• Functional Keywords: photopharmacology, microtubule dynamics, cytoskeleton, tubulin polymerisation inhibitor, colchicine, antimitotic, azobenzene, cell division, cell cycle, spatiotemporal control
• Biological source: synthetic construct; More
• Total number of polymer chains: 3
• Total formula weight: 119548.82

Authors

Wranik, M.,Weinert, T.,Olieric, N.,Gao, L.,Kraus, Y.C.M.,Bingham, R.,Ntouliou, E.,Ahlfeld, J.,Thorn-Seshold, O.,Steinmetz, M.O.,Standfuss, J. (deposition date: 2020-07-28, release date: 2020-12-23, Last modification date: 2024-01-31)

Primary citation

Gao, L.,Meiring, J.C.M.,Kraus, Y.,Wranik, M.,Weinert, T.,Pritzl, S.D.,Bingham, R.,Ntouliou, E.,Jansen, K.I.,Olieric, N.,Standfuss, J.,Kapitein, L.C.,Lohmuller, T.,Ahlfeld, J.,Akhmanova, A.,Steinmetz, M.O.,Thorn-Seshold, O.
A Robust, GFP-Orthogonal Photoswitchable Inhibitor Scaffold Extends Optical Control over the Microtubule Cytoskeleton.
Cell Chem Biol, 28:228-, 2021

PubMed Abstract: 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.

PubMed: 33275880
DOI: 10.1016/j.chembiol.2020.11.007

Experimental method

X-RAY DIFFRACTION (1.747 Å)