Biochemical Analysis of Bacterial Condensins

Petrushenko, Zoya M.; Rybenkov, Valentin V.

doi:10.1007/978-1-4939-7098-8_12

Cited by 1 publication

(2 citation statements)

References 21 publications

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“…DNA bridging was assessed using a magnetic bead pull down assay as previously described 50 in a reaction buffer containing 20 mM HEPES, pH 7.7, 50 mM NaCl, 2 mM MgCl 2 , 5% glycerol, and 1 mM DTT and the indicated compounds.…”

Section: Methodsmentioning

confidence: 99%

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Small Molecule Condensin Inhibitors

et al. 2018

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Condensins play a unique role in orchestrating the global folding of the chromosome, an essential cellular process, and contribute to human disease and bacterial pathogenicity. As such, they represent an attractive and as yet untapped target for diverse therapeutic interventions. We describe here the discovery of small molecule inhibitors of the Escherichia coli condensin MukBEF. Pilot screening of a small diversity set revealed five compounds that inhibit the MukBEF pathway, two of which, Michellamine B and NSC260594, affected MukB directly. Computer-assisted docking suggested plausible binding sites for the two compounds in the hinge and head domains of MukB, and both binding sites were experimentally validated using mutational analysis and inspection of NSC260594 analogs. These results outline a strategy for the discovery of condensin inhibitors, identify druggable binding sites on the protein, and describe two small molecule inhibitors of condensins.

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Section: Methodsmentioning

confidence: 99%

“…For the protein aggregation assay, 2 μ g of protein was incubated for 10 min at 23 °C in 25 μ L of reaction buffer supplemented with compounds and then fractionated by low speed centrifugation as described in ref 50.…”

Section: Methodsmentioning

confidence: 99%