8CLH

Drug cocktail (Colchicine, Epothilone A, Peloruside, Ansamitocin P3, Vinblastine) bound to tubulin (T2R-TTL) complex

Summary for 8CLH

• Entry DOI: 10.2210/pdb8clh/pdb
• Descriptor: Tubulin alpha-1B chain, EPOTHILONE A, Peloruside A, ... (15 entities in total)
• Functional Keywords: drug-tubulin-complex cell cycle inhibition, cell cycle
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 6
• Total formula weight: 260696.54

Authors

Wranik, M.,Bertrand, Q.,Kepa, M.W.,Weinert, T.,Steinmetz, M.,Standfuss, J. (deposition date: 2023-02-16, release date: 2023-12-13)

Primary citation

Wranik, M.,Kepa, M.W.,Beale, E.V.,James, D.,Bertrand, Q.,Weinert, T.,Furrer, A.,Glover, H.,Gashi, D.,Carrillo, M.,Kondo, Y.,Stipp, R.T.,Khusainov, G.,Nass, K.,Ozerov, D.,Cirelli, C.,Johnson, P.J.M.,Dworkowski, F.,Beale, J.H.,Stubbs, S.,Zamofing, T.,Schneider, M.,Krauskopf, K.,Gao, L.,Thorn-Seshold, O.,Bostedt, C.,Bacellar, C.,Steinmetz, M.O.,Milne, C.,Standfuss, J.
A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.
Nat Commun, 14:7956-7956, 2023

PubMed Abstract: Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs. Compared to a standard single extruder, sample exchange time was halved and the workload of users was greatly reduced. In-built temperature control of samples facilitated optimal extrusion and supported sample stability. After commissioning the device with lysozyme crystals, we collected time-resolved data using crystals of a membrane-bound, light-driven sodium pump. Static data were also collected from the soluble protein tubulin that was soaked with a series of small molecule drugs. Using these data, we identify low occupancy (as little as 30%) ligands using a minimal amount of data from a serial crystallography experiment, a result that could be exploited for structure-based drug design.

PubMed: 38042952
DOI: 10.1038/s41467-023-43523-5

Experimental method

X-RAY DIFFRACTION (2.5 Å)