8C3J
Stapled peptide SP2 in complex with humanised RadA mutant HumRadA22
Summary for 8C3J
| Entry DOI | 10.2210/pdb8c3j/pdb |
| Descriptor | DNA repair and recombination protein RadA, Breast cancer type 2 susceptibility protein, 2-[(4,6-diethyl-1,3,5-triazin-2-yl)-methyl-amino]ethanoic acid (3 entities in total) |
| Functional Keywords | stapled peptide, rad51, brca2, brc repeat, recombination |
| Biological source | Pyrococcus furiosus More |
| Total number of polymer chains | 4 |
| Total formula weight | 58682.71 |
| Authors | Pantelejevs, T.,Hyvonen, M. (deposition date: 2022-12-26, release date: 2023-11-29, Last modification date: 2024-11-13) |
| Primary citation | Pantelejevs, T.,Zuazua-Villar, P.,Koczy, O.,Counsell, A.J.,Walsh, S.J.,Robertson, N.S.,Spring, D.R.,Downs, J.A.,Hyvonen, M. A recombinant approach for stapled peptide discovery yields inhibitors of the RAD51 recombinase. Chem Sci, 14:13915-13923, 2023 Cited by PubMed Abstract: Stapling is a macrocyclisation method that connects amino acid side chains of a peptide to improve its pharmacological properties. We describe an approach for stapled peptide preparation and biochemical evaluation that combines recombinant expression of fusion constructs of target peptides and cysteine-reactive divinyl-heteroaryl chemistry as an alternative to solid-phase synthesis. We then employ this workflow to prepare and evaluate BRC-repeat-derived inhibitors of the RAD51 recombinase, showing that a diverse range of secondary structure elements in the BRC repeat can be stapled without compromising binding and function. Using X-ray crystallography, we elucidate the atomic-level features of the staple moieties. We then demonstrate that BRC-repeat-derived stapled peptides can disrupt RAD51 function in cells following ionising radiation treatment. PubMed: 38075664DOI: 10.1039/d3sc03331g PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.02 Å) |
Structure validation
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