View source for 7gyl


==Crystal Structure of HSP72 in complex with ligand 11 at 4.29 MGy X-ray dose==
<StructureSection load='7gyl' size='340' side='right'caption='[[7gyl]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7gyl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7GYL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7GYL 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]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PS:3-PYRIDINIUM-1-YLPROPANE-1-SULFONATE'>1PS</scene>, <scene name='pdbligand=A1ACZ:8-chloroadenosine'>A1ACZ</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7gyl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7gyl OCA], [https://pdbe.org/7gyl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7gyl RCSB], [https://www.ebi.ac.uk/pdbsum/7gyl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7gyl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HS71A_HUMAN HS71A_HUMAN] In cooperation with other chaperones, Hsp70s stabilize preexistent proteins against aggregation and mediate the folding of newly translated polypeptides in the cytosol as well as within organelles. These chaperones participate in all these processes through their ability to recognize nonnative conformations of other proteins. They bind extended peptide segments with a net hydrophobic character exposed by polypeptides during translation and membrane translocation, or following stress-induced damage. In case of rotavirus A infection, serves as a post-attachment receptor for the virus to facilitate entry into the cell. Essential for STUB1-mediated ubiquitination and degradation of FOXP3 in regulatory T-cells (Treg) during inflammation (PubMed:23973223).<ref>PMID:16537599</ref> <ref>PMID:22528486</ref> <ref>PMID:23973223</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein-inhibitor crystal structures aid medicinal chemists in efficiently improving the potency and selectivity of small-molecule inhibitors. It is estimated that a quarter of lead molecules in drug discovery projects are halogenated. Protein-inhibitor crystal structures have shed light on the role of halogen atoms in ligand binding. They form halogen bonds with protein atoms and improve shape complementarity of inhibitors with protein binding sites. However, specific radiation damage (SRD) can cause cleavage of carbon-halogen (C-X) bonds during X-ray diffraction data collection. This study shows significant C-X bond cleavage in protein-ligand structures of the therapeutic cancer targets B-cell lymphoma 6 (BCL6) and heat shock protein 72 (HSP72) complexed with halogenated ligands, which is dependent on the type of halogen and chemical structure of the ligand. The study found that metrics used to evaluate the fit of the ligand to the electron density deteriorated with increasing X-ray dose, and that SRD eliminated the anomalous signal from brominated ligands. A point of diminishing returns is identified, where collecting highly redundant data reduces the anomalous signal that may be used to identify binding sites of low-affinity ligands or for experimental phasing. Straightforward steps are proposed to mitigate the effects of C-X bond cleavage on structures of proteins bound to halogenated ligands and to improve the success of anomalous scattering experiments.

Specific radiation damage to halogenated inhibitors and ligands in protein-ligand crystal structures.,Rodrigues MJ, Cabry M, Collie G, Carter M, McAndrew C, Owen RL, Bellenie BR, Le Bihan YV, van Montfort RLM J Appl Crystallogr. 2024 Nov 26;57(Pt 6):1951-1965. doi: , 10.1107/S1600576724010549. eCollection 2024 Dec 1. PMID:39628887<ref>PMID:39628887</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7gyl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cabry M]]
[[Category: Le Bihan YV]]
[[Category: Rodrigues MJ]]
[[Category: Van Montfort RLM]]