3esk: Difference between revisions
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<StructureSection load='3esk' size='340' side='right'caption='[[3esk]], [[Resolution|resolution]] 2.05Å' scene=''> | <StructureSection load='3esk' size='340' side='right'caption='[[3esk]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3esk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3esk]] is a 2 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=3ESK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ESK FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=3esk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3esk OCA], [https://pdbe.org/3esk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3esk RCSB], [https://www.ebi.ac.uk/pdbsum/3esk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3esk 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=3esk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3esk OCA], [https://pdbe.org/3esk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3esk RCSB], [https://www.ebi.ac.uk/pdbsum/3esk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3esk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/STIP1_HUMAN STIP1_HUMAN] Mediates the association of the molecular chaperones HSC70 and HSP90 (HSPCA and HSPCB). | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Kajander | [[Category: Kajander T]] | ||
[[Category: Regan | [[Category: Regan L]] | ||
Latest revision as of 09:32, 6 September 2023
Structure of HOP TPR2A domain in complex with the non-cognate Hsc70 peptide ligandStructure of HOP TPR2A domain in complex with the non-cognate Hsc70 peptide ligand
Structural highlights
FunctionSTIP1_HUMAN Mediates the association of the molecular chaperones HSC70 and HSP90 (HSPCA and HSPCB). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe Hsp-organizing protein (HOP) binds to the C termini of the chaperones Hsp70 and Hsp90, thus bringing them together so that substrate proteins can be passed from Hsp70 to Hsp90. Because Hsp90 is essential for the correct folding and maturation of many oncogenic proteins, it has become a significant target for anti-cancer drug design. HOP binds to Hsp70 and Hsp90 via two independent tetratricopeptide (TPR) domains, TPR1 and TPR2A, respectively. We have analyzed ligand binding using Poisson-Boltzmann continuum electrostatic calculations, free energy perturbation, molecular dynamics simulations, and site-directed mutagenesis to delineate the contribution of different interactions to the affinity and specificity of the TPR-peptide interactions. We found that continuum electrostatic calculations could be used to guide protein design by removing unfavorable interactions to increase binding affinity, with an 80-fold increase in affinity for TPR2A. Contributions at buried charged residues, however, were better predicted by free energy perturbation calculations. We suggest using a combination of the two approaches for increasing the accuracy of results, with free energy perturbation calculations used only at selected buried residues of the ligand binding pocket. Finally we present the crystal structure of TPR2A in complex with its non-cognate Hsp70 ligand, which provides insight on the origins of specificity in TPR domain-peptide recognition. Electrostatic interactions of Hsp-organizing protein tetratricopeptide domains with Hsp70 and Hsp90: computational analysis and protein engineering.,Kajander T, Sachs JN, Goldman A, Regan L J Biol Chem. 2009 Sep 11;284(37):25364-74. Epub 2009 Jul 7. PMID:19586912[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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