1uyc: Difference between revisions
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<StructureSection load='1uyc' size='340' side='right'caption='[[1uyc]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='1uyc' size='340' side='right'caption='[[1uyc]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1uyc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[1uyc]] 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=1UYC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UYC 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]] 2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PU7:9-BUTYL-8-(2,5-DIMETHOXY-BENZYL)-9H-PURIN-6-YLAMINE'>PU7</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=1uyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uyc OCA], [https://pdbe.org/1uyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uyc RCSB], [https://www.ebi.ac.uk/pdbsum/1uyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uyc 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=1uyc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uyc OCA], [https://pdbe.org/1uyc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uyc RCSB], [https://www.ebi.ac.uk/pdbsum/1uyc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uyc ProSAT]</span></td></tr> | ||
</table> | </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> | |||
== 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: Aherne | [[Category: Aherne W]] | ||
[[Category: Barril | [[Category: Barril X]] | ||
[[Category: Beswick | [[Category: Beswick M]] | ||
[[Category: Boxall | [[Category: Boxall K]] | ||
[[Category: Collier | [[Category: Collier A]] | ||
[[Category: Davies | [[Category: Davies N]] | ||
[[Category: Drysdale | [[Category: Drysdale M]] | ||
[[Category: Dymock | [[Category: Dymock B]] | ||
[[Category: Fink | [[Category: Fink A]] | ||
[[Category: Fromont | [[Category: Fromont C]] | ||
[[Category: Hubbard | [[Category: Hubbard RE]] | ||
[[Category: Massey | [[Category: Massey A]] | ||
[[Category: Sharp | [[Category: Sharp S]] | ||
[[Category: Sheridan | [[Category: Sheridan L]] | ||
[[Category: Surgenor | [[Category: Surgenor A]] | ||
[[Category: Workman | [[Category: Workman P]] | ||
[[Category: Wright | [[Category: Wright L]] | ||
Latest revision as of 16:04, 13 December 2023
Human Hsp90-alpha with 9-Butyl-8-(2,5-dimethoxy-benzyl)-9H-purin-6-ylamineHuman Hsp90-alpha with 9-Butyl-8-(2,5-dimethoxy-benzyl)-9H-purin-6-ylamine
Structural highlights
FunctionHS90A_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.[1] [2] 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 PubMedInhibition of the ATPase activity of the chaperone protein HSP90 is a potential strategy for treatment of cancers. We have determined structures of the HSP90alpha N-terminal domain complexed with the purine-based inhibitor, PU3, and analogs with enhanced potency both in enzyme and cell-based assays. The compounds induce upregulation of HSP70 and downregulation of the known HSP90 client proteins Raf-1, CDK4, and ErbB2, confirming that the molecules inhibit cell growth by a mechanism dependent on HSP90 inhibition. We have also determined the first structure of the N-terminal domain of HSP90beta, complexed with PU3. The structures allow a detailed rationale to be developed for the observed affinity of the PU3 class of compounds for HSP90 and also provide a structural framework for design of compounds with improved binding affinity and drug-like properties. Structure-activity relationships in purine-based inhibitor binding to HSP90 isoforms.,Wright L, Barril X, Dymock B, Sheridan L, Surgenor A, Beswick M, Drysdale M, Collier A, Massey A, Davies N, Fink A, Fromont C, Aherne W, Boxall K, Sharp S, Workman P, Hubbard RE Chem Biol. 2004 Jun;11(6):775-85. PMID:15217611[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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