9F8G
Photostatin (photoswitchable azo-combretastatin) Z-PST27 bound to tubulin-DARPin D1 complex
This is a non-PDB format compatible entry.
Summary for 9F8G
| Entry DOI | 10.2210/pdb9f8g/pdb |
| Descriptor | Tubulin alpha-1B chain, Tubulin beta-2B chain, Designed Ankyrin Repeat Protein (DARPIN) D1, ... (8 entities in total) |
| Functional Keywords | tubulin polymerisation inhibitor, microtubule dynamics, antimitotics, photopharmacology, photoswitch, sensitisation, cell cycle |
| Biological source | Bos taurus (cattle) More |
| Total number of polymer chains | 3 |
| Total formula weight | 119706.20 |
| Authors | |
| Primary citation | Reynders, M.,Garscia, M.,Muller-Deku, A.,Wranik, M.,Krauskopf, K.,de la Osa de la Rosa, L.,Schaffer, K.,Jotten, A.,Rode, A.,Stierle, V.,Kraus, Y.,Baumgartner, B.,Ali, A.,Bubeneck, A.,Seal, T.,Steinmetz, M.O.,Paulitschke, P.,Thorn-Seshold, O. A photo-SAR study of photoswitchable azobenzene tubulin-inhibiting antimitotics identifying a general method for near-quantitative photocontrol. Chem Sci, 15:12301-12309, 2024 Cited by PubMed Abstract: Azobenzene analogues of the tubulin polymerisation inhibitor combretastatin A4 (PSTs) were previously developed to optically control microtubule dynamics in living systems, with subsecond response time and single-cell spatial precision, by reversible photoswitching of their bioactivity with near-UV/visible light. First-generation PSTs were sufficiently potent and photoswitchable for use in live cells and embryos. However, the link between their seconds-scale and hours-scale bioactivity remained untested. Furthermore, the scope for modifications to tune their photo-structure-activity-relationship or expand their function was unknown. Here, we used large-field-of-view, long-term tandem photoswitching/microscopy to reveal the temporal onset of cytostatic effects. We then synthesised a panel of novel PSTs exploring structural variations that tune photoresponse wavelengths and lipophilicity, identifying promising blue-shifted analogues that are better-compatible with GFP/YFP imaging. Taken together, these results can guide new design and applications for photoswitchable microtubule inhibitors. We also identified tolerated sites for linkers to attach functional cargos; and we tested fluorophores, aiming at RET isomerisation or reporter probes. Instead we found that these antennas greatly enhance long-wavelength single-photon photoisomerisation, by an as-yet un-explored mechanism, that can now drive general progress towards near-quantitative long-wavelength photoswitching of photopharmaceuticals in living systems, with minimal molecular redesign and broad scope. PubMed: 39118608DOI: 10.1039/d4sc03072a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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