Engineering Archeal Surrogate Systems for the Development of Protein-Protein Interaction Inhibitors against Human RAD51

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Engineering Archeal Surrogate Systems for the Development of Protein-Protein Interaction Inhibitors against Human RAD51

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作者：Tommaso Moschetti¹ ; Timothy Sharpe¹ ; ⁴ ; Gerhard Fischer¹ ; May E. Marsh¹ ; Hong Kin Ng¹ ; Matthew Morgan¹ ; Duncan E. Scott² ; Tom L. Blundell¹ ; Ashok R. Venkitaraman³ ; John Skidmore² ; Chris Abell² ; Marko Hyv&ouml ; nen¹ ; ^{mh256@cam.ac.uk" class="auth_mail" title="E-mail the corresponding author}
关键词：PPI ; protein&ndash ; protein interaction ; HR ; homologous recombination ; NF ; nucleoprotein filament ; BRC4 ; fourth BRC repeat ; HumRadA1 ; first humanised RadA protein ; DSF ; differential scanning fluorimetry ; ITC ; isothermal titration calorimetry ; FP ; fluorescence polarisation ; GST ; glutathione S-transferase ; DLS ; dynamic light scattering ; PEG ; polyethylene glycol ; TEV ; tobacco etch mosaic virus ; DMSO ; dimethyl sulphoxide
刊名：Journal of Molecular Biology
出版年：2016
出版时间：20 November 2016
年：2016
卷：428
期：23
页码：4589-4607
全文大小：2461 K

文摘

•: Archeal RadA, humanised to resemble RAD51, binds the fourth BRC repeat with high affinity.
•: Chimeric archeal/human RAD51 shows increased thermal stability.
•: Robust crystallographic system enables fragment-based drug discovery against RAD51.
•: Dedicated surrogate proteins were needed for different assays.

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