This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


5fos

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (07:47, 7 February 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
==HUMANISED MONOMERIC RADA IN COMPLEX WITH OLIGOMERISATION PEPTIDE==
==HUMANISED MONOMERIC RADA IN COMPLEX WITH OLIGOMERISATION PEPTIDE==
-
<StructureSection load='5fos' size='340' side='right' caption='[[5fos]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
+
<StructureSection load='5fos' size='340' side='right'caption='[[5fos]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5fos]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FOS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FOS FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5fos]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pyrococcus_furiosus Pyrococcus furiosus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FOS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FOS FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 1.35&#8491;</td></tr>
-
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fot|5fot]], [[5fou|5fou]], [[5fov|5fov]], [[5fow|5fow]], [[5fox|5fox]]</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=5fos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fos OCA], [https://pdbe.org/5fos PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fos RCSB], [https://www.ebi.ac.uk/pdbsum/5fos PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fos ProSAT]</span></td></tr>
-
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5fos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fos OCA], [http://pdbe.org/5fos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fos RCSB], [http://www.ebi.ac.uk/pdbsum/5fos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fos ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://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>
+
==See Also==
-
 
+
*[[Resolvase 3D structures|Resolvase 3D structures]]
-
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+
-
</div>
+
-
<div class="pdbe-citations 5fos" style="background-color:#fffaf0;"></div>
+
-
== References ==
+
-
<references/>
+
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Abell, C]]
+
[[Category: Large Structures]]
-
[[Category: Blundell, T L]]
+
[[Category: Pyrococcus furiosus]]
-
[[Category: Fischer, G]]
+
[[Category: Abell C]]
-
[[Category: Hyvonen, M]]
+
[[Category: Blundell TL]]
-
[[Category: Marsh, M]]
+
[[Category: Fischer G]]
-
[[Category: Moschetti, T]]
+
[[Category: Hyvonen M]]
-
[[Category: Sharpe, T]]
+
[[Category: Marsh M]]
-
[[Category: Fxxa motif]]
+
[[Category: Moschetti T]]
-
[[Category: Hydrolase]]
+
[[Category: Sharpe T]]
-
[[Category: Recombinase]]
+

Current revision

HUMANISED MONOMERIC RADA IN COMPLEX WITH OLIGOMERISATION PEPTIDE

PDB ID 5fos

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5fos"
Personal tools