View source for 6tw4


==HumRadA22F in complex with compound 6==
<StructureSection load='6tw4' size='340' side='right'caption='[[6tw4]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6tw4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_furiosus_DSM_3638 Pyrococcus furiosus DSM 3638]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TW4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TW4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NZW:~{N}-[2-[(2~{S})-2-[[(1~{S})-1-(4-methoxyphenyl)ethyl]carbamoyl]pyrrolidin-1-yl]-2-oxidanylidene-ethyl]quinoline-2-carboxamide'>NZW</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6tw4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tw4 OCA], [https://pdbe.org/6tw4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tw4 RCSB], [https://www.ebi.ac.uk/pdbsum/6tw4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tw4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RADA_PYRFU RADA_PYRFU] Involved in DNA repair and in homologous recombination. Binds and assemble on single-stranded DNA to form a nucleoprotein filament. Hydrolyzes ATP in a ssDNA-dependent manner and promotes DNA strand exchange between homologous DNA molecules.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
BRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using structure-guided molecular design, templated on a monomeric thermostable chimera between human RAD51 and archaeal RadA, we identify CAM833, a 529 Da orthosteric inhibitor of RAD51:BRC with a Kd of 366 nM. The quinoline of CAM833 occupies a hotspot, the Phe-binding pocket on RAD51 and the methyl of the substituted alpha-methylbenzyl group occupies the Ala-binding pocket. In cells, CAM833 diminishes formation of damage-induced RAD51 nuclear foci; inhibits RAD51 molecular clustering, suppressing extended RAD51 filament assembly; potentiates cytotoxicity by ionizing radiation, augmenting 4N cell-cycle arrest and apoptotic cell death and works with poly-ADP ribose polymerase (PARP)1 inhibitors to suppress growth in BRCA2-wildtype cells. Thus, chemical inhibition of the protein-protein interaction between BRCA2 and RAD51 disrupts HDR and potentiates DNA damage-induced cell death, with implications for cancer therapy.

A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death.,Scott DE, Francis-Newton NJ, Marsh ME, Coyne AG, Fischer G, Moschetti T, Bayly AR, Sharpe TD, Haas KT, Barber L, Valenzano CR, Srinivasan R, Huggins DJ, Lee M, Emery A, Hardwick B, Ehebauer M, Dagostin C, Esposito A, Pellegrini L, Perrior T, McKenzie G, Blundell TL, Hyvonen M, Skidmore J, Venkitaraman AR, Abell C Cell Chem Biol. 2021 Mar 1. pii: S2451-9456(21)00058-1. doi:, 10.1016/j.chembiol.2021.02.006. PMID:33662256<ref>PMID:33662256</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6tw4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pyrococcus furiosus DSM 3638]]
[[Category: Abell C]]
[[Category: Coyne AG]]
[[Category: Hyvonen M]]
[[Category: Marsh ME]]
[[Category: Scott DE]]
[[Category: Skidmore J]]