5lrl: Difference between revisions

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<StructureSection load='5lrl' size='340' side='right'caption='[[5lrl]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
<StructureSection load='5lrl' size='340' side='right'caption='[[5lrl]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5lrl]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LRL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LRL FirstGlance]. <br>
<table><tr><td colspan='2'>[[5lrl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LRL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LRL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=73S:2-azanyl-5-chloranyl-~{N}-[(9~{R})-4-(1~{H}-imidazo[4,5-c]pyridin-2-yl)-9~{H}-fluoren-9-yl]pyrimidine-4-carboxamide'>73S</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=73S:2-azanyl-5-chloranyl-~{N}-[(9~{R})-4-(1~{H}-imidazo[4,5-c]pyridin-2-yl)-9~{H}-fluoren-9-yl]pyrimidine-4-carboxamide'>73S</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HSP90AA1, HSP90A, HSPC1, HSPCA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5lrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lrl OCA], [http://pdbe.org/5lrl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lrl RCSB], [http://www.ebi.ac.uk/pdbsum/5lrl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lrl 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=5lrl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lrl OCA], [https://pdbe.org/5lrl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lrl RCSB], [https://www.ebi.ac.uk/pdbsum/5lrl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lrl ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>   
[[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 ==
We here report on nonequilibrium targeted molecular dynamics simulations as a tool for the estimation of protein-ligand unbinding kinetics. Correlating simulations with experimental data from SPR kinetics measurements and X-ray crystallography on two small molecule compound libraries bound to the N-terminal domain of the chaperone Hsp90, we show that the mean nonequilibrium work computed in an ensemble of trajectories of enforced ligand unbinding is a promising predictor for ligand unbinding rates. We furthermore investigate the molecular basis determining unbinding rates within the compound libraries. We propose ligand conformational changes and protein-ligand nonbonded interactions to impact on unbinding rates. Ligands may remain longer at the protein if they exhibit strong electrostatic and/or van der Waals interactions with the target. In the case of ligands with a rigid chemical scaffold that exhibit longer residence times, transient electrostatic interactions with the protein appear to facilitate unbinding. Our results imply that understanding the unbinding pathway and the protein-ligand interactions along this path is crucial for the prediction of small molecule ligands with defined unbinding kinetics.
 
Estimation of Protein-Ligand Unbinding Kinetics Using Non-Equilibrium Targeted Molecular Dynamics Simulations.,Wolf S, Amaral M, Lowinski M, Vallee F, Musil D, Guldenhaupt J, Dreyer MK, Bomke J, Frech M, Schlitter J, Gerwert K J Chem Inf Model. 2019 Dec 23;59(12):5135-5147. doi: 10.1021/acs.jcim.9b00592., Epub 2019 Nov 22. PMID:31697501<ref>PMID:31697501</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lrl" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Heat Shock Proteins|Heat Shock Proteins]]
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
== References ==
== References ==
<references/>
<references/>
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