5j2x: Difference between revisions
New page: '''Unreleased structure''' The entry 5j2x is ON HOLD Authors: Amaral, M., Matias, P. Description: Crystal Structure of Hsp90-alpha N-domain in complex with 5-(5-Bromo-2,4-dihydroxy-phe... |
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==Crystal Structure of Hsp90-alpha N-domain in complex with 5-(5-Bromo-2,4-dihydroxy-phenyl)-4-(2-fluoro-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one== | |||
<StructureSection load='5j2x' size='340' side='right'caption='[[5j2x]], [[Resolution|resolution]] 1.22Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5j2x]] 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=5J2X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J2X 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]] 1.22Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DL:5-(5-Bromo-2,4-dihydroxy-phenyl)-4-(2-fluoro-phenyl)-2,4-dihydro-[1,2,4]triazol-3-one'>6DL</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=5j2x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j2x OCA], [https://pdbe.org/5j2x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j2x RCSB], [https://www.ebi.ac.uk/pdbsum/5j2x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j2x 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 == | |||
Structure-based drug design has often been restricted by the rather static picture of protein-ligand complexes presented by crystal structures, despite the widely accepted importance of protein flexibility in biomolecular recognition. Here we report a detailed experimental and computational study of the drug target, human heat shock protein 90, to explore the contribution of protein dynamics to the binding thermodynamics and kinetics of drug-like compounds. We observe that their binding properties depend on whether the protein has a loop or a helical conformation in the binding site of the ligand-bound state. Compounds bound to the helical conformation display slow association and dissociation rates, high-affinity and high cellular efficacy, and predominantly entropically driven binding. An important entropic contribution comes from the greater flexibility of the helical relative to the loop conformation in the ligand-bound state. This unusual mechanism suggests increasing target flexibility in the bound state by ligand design as a new strategy for drug discovery. | |||
Protein conformational flexibility modulates kinetics and thermodynamics of drug binding.,Amaral M, Kokh DB, Bomke J, Wegener A, Buchstaller HP, Eggenweiler HM, Matias P, Sirrenberg C, Wade RC, Frech M Nat Commun. 2017 Dec 22;8(1):2276. doi: 10.1038/s41467-017-02258-w. PMID:29273709<ref>PMID:29273709</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5j2x" style="background-color:#fffaf0;"></div> | ||
[[Category: Amaral | |||
==See Also== | |||
*[[Heat Shock Protein structures|Heat Shock Protein structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Amaral M]] | |||
[[Category: Matias P]] | |||