5j4h: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5j4h]] 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=5J4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J4H FirstGlance]. <br>
<table><tr><td colspan='2'>[[5j4h]] 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=5J4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J4H FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1F1:1H-INDOLE-6-CARBOXYLIC+ACID'>1F1</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.374&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1F1:1H-INDOLE-6-CARBOXYLIC+ACID'>1F1</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=5j4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j4h OCA], [https://pdbe.org/5j4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j4h RCSB], [https://www.ebi.ac.uk/pdbsum/5j4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j4h ProSAT]</span></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=5j4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j4h OCA], [https://pdbe.org/5j4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j4h RCSB], [https://www.ebi.ac.uk/pdbsum/5j4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j4h ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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.
[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 ==
Protein-protein interactions (PPIs) are increasingly important targets for drug discovery. Efficient fragment-based drug discovery approaches to tackle PPIs are often stymied by difficulties in the production of stable, unliganded target proteins. Here, we report an approach that exploits protein engineering to 'humanise' thermophilic archeal surrogate proteins as targets for small molecule inhibitor discovery, and exemplify this approach in the development of inhibitors against the PPI between the recombinase RAD51 and tumour suppressor BRCA2. As human RAD51 has proved impossible to produce in a form that is compatible with the requirements of fragment-based drug discovery, we have developed a surrogate protein system using RadA from Pyrococcus furiosus. Using a monomerised RadA as our starting point, we have adopted two parallel and mutually instructive approaches to mimic the human enzyme: firstly by mutating RadA to increase sequence identity with RAD51 in the BRC repeat binding sites, and secondly by generating a chimeric archaeal-human protein. Both approaches generate proteins that interact with a BRC4 repeat with affinity and stoichiometry comparable to human RAD51. Stepwise humanisation has also allowed us to elucidate the determinants of RAD51 binding to BRC repeats and the contributions of key interacting residues to this interaction. These surrogate proteins have enabled the development of biochemical and biophysical assays in our ongoing fragment-based small molecule inhibitor programme and they have allowed us to determine hundreds of liganded structures in support of our structure-guided design process, demonstrating the feasibility and advantages of using archeal surrogates to overcome difficulties in handling human proteins.
Engineering archeal surrogate systems for the development of protein-protein interaction inhibitors against human RAD51.,Moschetti T, Sharpe T, Fischer G, Marsh ME, Ng H, Morgan M, Scott D, Blundell TL, Venkitaraman A, Skidmore J, Abell C, Hyvonen M J Mol Biol. 2016 Oct 7. pii: S0022-2836(16)30424-7. doi:, 10.1016/j.jmb.2016.10.009. PMID:27725183<ref>PMID:27725183</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5j4h" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Resolvase 3D structures|Resolvase 3D structures]]
*[[Resolvase 3D structures|Resolvase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 10:24, 1 May 2024

Structure of humanised RadA-mutant humRadA22F in complex with indole-6-carboxylic acidStructure of humanised RadA-mutant humRadA22F in complex with indole-6-carboxylic acid

Structural highlights

5j4h is a 1 chain structure with sequence from Pyrococcus furiosus DSM 3638. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.374Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

See Also

5j4h, resolution 1.37Å

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