View source for 7s8y


==Cryogenic apo Human Hsp90a-NTD==
<StructureSection load='7s8y' size='340' side='right'caption='[[7s8y]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7s8y]] 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=7S8Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S8Y 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]] 1.59&#8491;</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=7s8y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s8y OCA], [https://pdbe.org/7s8y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s8y RCSB], [https://www.ebi.ac.uk/pdbsum/7s8y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s8y ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HS90A_HUMAN HS90A_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.<ref>PMID:15937123</ref> <ref>PMID:11274138</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
High-resolution crystal structures highlight the importance of water networks in protein-ligand interactions. However, as these are typically determined at cryogenic temperature, resulting insights may be structurally precise but not biologically accurate. By collecting 10 matched room-temperature and cryogenic datasets of the biomedical target Hsp90alpha, we identified changes in water networks that impact protein conformations at the ligand binding interface. Water repositioning with temperature repopulates protein ensembles and ligand interactions. We introduce Flipper conformational barcodes to identify temperature-sensitive regions in electron density maps. This revealed that temperature-responsive states coincide with ligand-responsive regions and capture unique binding signatures that disappear upon cryo-cooling. Our results have implications for discovering Hsp90 selective ligands, and, more generally, for the utility of hidden protein and water conformations in drug discovery.

Water Networks Repopulate Protein-Ligand Interfaces with Temperature.,Stachowski TR, Vanarotti M, Seetharaman J, Lopez K, Fischer M Angew Chem Int Ed Engl. 2022 Aug 1;61(31):e202112919. doi:, 10.1002/anie.202112919. Epub 2022 Jun 21. PMID:35648650<ref>PMID:35648650</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7s8y" style="background-color:#fffaf0;"></div>

==See Also==
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fischer M]]
[[Category: Lopez K]]
[[Category: Stachowski TR]]
[[Category: Vanarotti M]]