Pan‐HSP90 ligand binding reveals isoform‐specific differences in plasticity and water networks

Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by...

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Vydáno v:	Protein science Ročník 32; číslo 5; s. e4629 - n/a
Hlavní autoři:	Stachowski, Timothy R., Nithianantham, Stanley, Vanarotti, Murugendra, Lopez, Karlo, Fischer, Marcus
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken, USA John Wiley & Sons, Inc 01.05.2023 Wiley Subscription Services, Inc
Témata:	Antineoplastic Agents - chemistry Binding conformational flexibility Heat shock proteins HSP90 Heat-Shock Proteins - chemistry Hsp90 isoforms Hsp90 protein Humans Isoforms ligand binding Ligands pan‐Hsp90 inhibitors Protein Binding Protein Conformation Protein folding Protein Isoforms - chemistry Proteins Side effects Therapeutic targets water networks Hsp90 isoforms conformational flexibility pan-Hsp90 inhibitors water networks ligand binding
ISSN:	0961-8368, 1469-896X, 1469-896X
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Abstract	Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan‐HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three‐pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side‐chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform‐ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an “old” target and reveal hidden isoform‐specific accommodations of congeneric ligands that may be exploited in ligand discovery and design. PDB Code(s): 7ULJ, 7ULL and 7ULK;
AbstractList	Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan‐HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three‐pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side‐chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform‐ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an “old” target and reveal hidden isoform‐specific accommodations of congeneric ligands that may be exploited in ligand discovery and design. PDB Code(s): 7ULJ, 7ULL and 7ULK; Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan‐HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three‐pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side‐chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform‐ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an “old” target and reveal hidden isoform‐specific accommodations of congeneric ligands that may be exploited in ligand discovery and design. PDB Code(s): 7ULJ , 7ULL and 7ULK ; Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan‐HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three‐pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side‐chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform‐ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an “old” target and reveal hidden isoform‐specific accommodations of congeneric ligands that may be exploited in ligand discovery and design. PDB Code(s): 7ULJ, 7ULL and 7ULK; Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan‐HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three‐pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side‐chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform‐ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an “old” target and reveal hidden isoform‐specific accommodations of congeneric ligands that may be exploited in ligand discovery and design. Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA-approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan-HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three-pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side-chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform-ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an "old" target and reveal hidden isoform-specific accommodations of congeneric ligands that may be exploited in ligand discovery and design.Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA-approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan-HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three-pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side-chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform-ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an "old" target and reveal hidden isoform-specific accommodations of congeneric ligands that may be exploited in ligand discovery and design.
Author	Nithianantham, Stanley Vanarotti, Murugendra Stachowski, Timothy R. Lopez, Karlo Fischer, Marcus
AuthorAffiliation	1 Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA 2 School of Natural Sciences, Mathematics, and Engineering California State University Bakersfield California 93311 USA
AuthorAffiliation_xml	– name: 2 School of Natural Sciences, Mathematics, and Engineering California State University Bakersfield California 93311 USA – name: 1 Department of Chemical Biology and Therapeutics St. Jude Children's Research Hospital Memphis Tennessee USA
Author_xml	– sequence: 1 givenname: Timothy R. orcidid: 0000-0002-6097-4857 surname: Stachowski fullname: Stachowski, Timothy R. organization: St. Jude Children's Research Hospital – sequence: 2 givenname: Stanley orcidid: 0000-0001-6238-647X surname: Nithianantham fullname: Nithianantham, Stanley organization: St. Jude Children's Research Hospital – sequence: 3 givenname: Murugendra orcidid: 0000-0003-4355-0283 surname: Vanarotti fullname: Vanarotti, Murugendra organization: St. Jude Children's Research Hospital – sequence: 4 givenname: Karlo orcidid: 0000-0002-6613-6547 surname: Lopez fullname: Lopez, Karlo organization: California State University – sequence: 5 givenname: Marcus orcidid: 0000-0002-7179-2581 surname: Fischer fullname: Fischer, Marcus email: marcus.fischer@stjude.org organization: St. Jude Children's Research Hospital
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Cites_doi	10.1002/cmdc.200900011 10.1039/D0SC04938G 10.1073/pnas.2011350117 10.1021/acs.jmedchem.7b01608 10.1002/pro.423 10.1016/S0968-0004(02)02067-4 10.1021/acschembio.6b00747 10.1038/s41467-017-02013-1 10.1074/jbc.RA119.009960 10.1158/1078-0432.CCR-13-2571 10.1016/j.apsb.2020.11.015 10.1021/ja303477g 10.1107/S0907444912044423 10.1093/nar/28.1.235 10.7554/eLife.74114 10.1016/j.ejmech.2022.114516 10.1016/j.bmcl.2013.11.036 10.1021/ja511893n 10.1039/D1SC02751D 10.1002/chem.201703398 10.1002/anie.202112919 10.1002/jcc.20084 10.1021/jm500042s 10.1073/pnas.1703287114 10.1002/cbic.201500196 10.1074/jbc.M308661200 10.1124/mi.9.1.7 10.1016/j.tibs.2014.12.002 10.1107/S2059798319011471 10.2174/156802609789895737 10.1038/nature04716 10.7554/eLife.25235 10.1021/acs.jmedchem.2c00708 10.1021/jacs.9b06275 10.1107/S0021889807021206 10.2174/1568026616666160413141154 10.1107/S0907444909047337 10.1002/prot.25750 10.1038/nsmb.1565 10.1021/acschembio.5b00683 10.1007/978-3-030-40204-4_9 10.1007/128_2011_181 10.1016/S0076-6879(97)76066-X 10.1038/s41467-017-02258-w 10.1016/j.bbamcr.2011.09.003 10.1073/pnas.1500806112 10.1021/acs.jmedchem.8b00105 10.2174/1389450120666190829162544 10.1016/j.ejmech.2021.113604 10.1107/S0907444910007493 10.1017/S0033583520000128 10.1016/j.sbi.2015.07.003 10.1038/nchembio.1335 10.1021/jm060297x 10.1021/acs.jmedchem.0c01700 10.1021/jm200350g 10.1038/nrc2887 10.1002/anie.202015422 10.2174/138161213804143725 10.1016/j.jmb.2009.03.071 10.1016/bs.acr.2015.12.001 10.1021/acs.jmedchem.7b00057 10.1038/nrc1716 10.1021/acschembio.8b00443 10.1021/jm900357y
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Copyright	2023 The Authors. published by Wiley Periodicals LLC on behalf of The Protein Society. 2023 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. 2023. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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References_xml	– volume: 87 start-page: 869 year: 2019 end-page: 77 article-title: Structures of Hsp90alpha and Hsp90beta bound to a purine‐scaffold inhibitor reveal an exploitable residue for drug selectivity publication-title: Proteins – volume: 11 year: 2022 article-title: Ligand binding remodels protein side‐chain conformational heterogeneity publication-title: elife – volume: 54 start-page: 3989 year: 2011 end-page: 4005 article-title: How well can fragments explore accessed chemical space? A case study from heat shock protein 90 publication-title: J Med Chem – volume: 9 start-page: 22 year: 2009 end-page: 30 article-title: Fragment‐based ligand discovery publication-title: Mol Interv – volume: 16 start-page: 287 year: 2009 end-page: 93 article-title: Dissection of the ATP‐induced conformational cycle of the molecular chaperone Hsp90 publication-title: Nat Struct Mol Biol – volume: 23 start-page: 15775 year: 2017 end-page: 82 article-title: Second generation Grp94‐selective inhibitors provide opportunities for the inhibition of metastatic cancer publication-title: Chemistry – volume: 13 start-page: 2522 year: 2018 end-page: 33 article-title: The recognition of unrelated ligands by individual proteins publication-title: ACS Chem Biol – volume: 12 start-page: 960 year: 2020 end-page: 8 article-title: Ligand design by targeting a binding site water publication-title: Chem Sci – volume: 57 start-page: 3382 year: 2014 end-page: 400 article-title: Identification of novel HSP90alpha/beta isoform selective inhibitors using structure‐based drug design. Demonstration of potential utility in treating CNS disorders such as Huntington's disease publication-title: J Med Chem – volume: 10 start-page: 2772 year: 2015 end-page: 84 article-title: The recognition of identical ligands by unrelated proteins publication-title: ACS Chem Biol – volume: 20 start-page: 275 year: 2014 end-page: 7 article-title: Stressing the development of small molecules targeting HSP90 publication-title: Clin Cancer Res – volume: 10 start-page: 537 year: 2010 end-page: 49 article-title: Targeting the dynamic HSP90 complex in cancer publication-title: Nat Rev Cancer – volume: 12 start-page: 11275 year: 2021 end-page: 93 article-title: Temperature artifacts in protein structures bias ligand‐binding predictions publication-title: Chem Sci – volume: 75 start-page: 861 year: 2019 end-page: 77 article-title: Macromolecular structure determination using X‐rays, neutrons and electrons: recent developments in Phenix publication-title: Acta Crystallogr D Struct Biol – volume: 21 start-page: 302 year: 2020 end-page: 17 article-title: Recent advances in the discovery of novel HSP90 inhibitors: an update from 2014 publication-title: Curr Drug Targets – volume: 19 start-page: 1420 year: 2010 end-page: 31 article-title: Automated electron‐density sampling reveals widespread conformational polymorphism in proteins publication-title: Protein Sci – volume: 40 start-page: 658 year: 2007 end-page: 74 article-title: Phaser crystallographic software publication-title: J Appl Crystallogr – volume: 52 start-page: 4794 year: 2009 end-page: 809 article-title: Combining hit identification strategies: fragment‐based and in silico approaches to orally active 2‐aminothieno[2,3‐d]pyrimidine inhibitors of the Hsp90 molecular chaperone publication-title: J Med Chem – volume: 60 start-page: 10547 year: 2021 end-page: 51 article-title: Selective inhibition of the Hsp90α isoform publication-title: Angew Chem Int Ed Engl – volume: 114 start-page: E6839 year: 2017 end-page: 46 article-title: Testing inhomogeneous solvation theory in structure‐based ligand discovery publication-title: Proc Natl Acad Sci U S A – volume: 294 start-page: 16010 year: 2019 end-page: 9 article-title: NECA derivatives exploit the paralog‐specific properties of the site 3 side pocket of Grp94, the endoplasmic reticulum Hsp90 publication-title: J Biol Chem – volume: 1823 start-page: 624 year: 2012 end-page: 35 article-title: The Hsp90 chaperone machinery: conformational dynamics and regulation by co‐chaperones publication-title: Biochim Biophys Acta – volume: 61 start-page: 2793 year: 2018 end-page: 805 article-title: Structure based design of a Grp94‐selective inhibitor: exploiting a key residue in Grp94 to optimize paralog‐selective binding publication-title: J Med Chem – volume: 61 year: 2022 article-title: Water networks repopulate protein‐ligand interfaces with temperature publication-title: Angew Chem Int Ed Engl – volume: 54 year: 2021 article-title: Macromolecular room temperature crystallography publication-title: Q Rev Biophys – volume: 9 start-page: 425 year: 2018 article-title: Structure‐guided design of an Hsp90β N‐terminal isoform‐selective inhibitor publication-title: Nat Commun – volume: 16 start-page: 1560 year: 2015 end-page: 4 article-title: One crystal, two temperatures: Cryocooling penalties Alter ligand binding to transient protein sites publication-title: Chembiochem – volume: 61 start-page: 5922 year: 2018 end-page: 5933 article-title: Paradoxically, most flexible ligand binds most entropy‐favored: intriguing impact of ligand flexibility and solvation on drug–kinase binding publication-title: J Med Chem – volume: 6 year: 2017 article-title: Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1 publication-title: elife – volume: 60 start-page: 6781 year: 2017 end-page: 827 article-title: The roles of water in the protein matrix: a largely untapped resource for drug discovery publication-title: J Med Chem – volume: 24 start-page: 204 year: 2014 end-page: 8 article-title: Correlation between chemotype‐dependent binding conformations of HSP90alpha/beta and isoform selectivity‐implications for the structure‐based design of HSP90alpha/beta selective inhibitors for treating neurodegenerative diseases publication-title: Bioorg Med Chem Lett – volume: 66 start-page: 486 year: 2010 end-page: 501 article-title: Features and development of Coot publication-title: Acta Crystallogr D Biol Crystallogr – volume: 69 start-page: 150 year: 2013 end-page: 67 article-title: Techniques, tools and best practices for ligand electron‐density analysis and results from their application to deposited crystal structures publication-title: Acta Crystallogr D Biol Crystallogr – volume: 49 start-page: 4953 year: 2006 end-page: 60 article-title: Structural and quantum chemical studies of 8‐aryl‐sulfanyl adenine class Hsp90 inhibitors publication-title: J Med Chem – volume: 16 start-page: 2779 year: 2016 end-page: 91 article-title: Paralog specific Hsp90 inhibitors—a brief history and a bright future publication-title: Curr Top Med Chem – year: 1993 – volume: 65 start-page: 13692 year: 2022 end-page: 704 article-title: Large‐scale ligand perturbations of the protein conformational landscape reveal state‐specific interaction hotspots publication-title: J Med Chem – volume: 238 year: 2022 article-title: Pan‐ and isoform‐specific inhibition of Hsp90: design strategy and recent advances publication-title: Eur J Med Chem – volume: 223 year: 2021 article-title: Design and synthesis of Grp94 selective inhibitors based on Phe199 induced fit mechanism and their anti‐inflammatory effects publication-title: Eur J Med Chem – volume: 19 start-page: 347 year: 2013 end-page: 65 article-title: The therapeutic target Hsp90 and cancer hallmarks publication-title: Curr Pharm Des – volume: 276 start-page: 307 year: 1997 end-page: 26 article-title: Processing of X‐ray diffraction data collected in oscillation mode publication-title: Methods Enzymol – volume: 9 start-page: 1436 year: 2009 end-page: 46 article-title: Purine‐scaffold Hsp90 inhibitors publication-title: Curr Top Med Chem – volume: 134 start-page: 9796 year: 2012 end-page: 804 article-title: Development of a Grp94 inhibitor publication-title: J Am Chem Soc – volume: 278 start-page: 48330 year: 2003 end-page: 8 article-title: Structure of the N‐terminal domain of GRP94. Basis for ligand specificity and regulation publication-title: J Biol Chem – volume: 1243 start-page: 135 year: 2020 end-page: 46 article-title: The right tool for the job: an overview of Hsp90 inhibitors publication-title: Adv Exp Med Biol – volume: 12 start-page: 244 year: 2017 end-page: 53 article-title: Transformation of the non‐selective Aminocyclohexanol‐based Hsp90 inhibitor into a Grp94‐Seletive scaffold publication-title: ACS Chem Biol – volume: 5 start-page: 761 year: 2005 end-page: 72 article-title: HSP90 and the chaperoning of cancer publication-title: Nat Rev Cancer – volume: 129 start-page: 51 year: 2016 end-page: 88 article-title: Anticancer inhibitors of Hsp90 function: beyond the usual suspects publication-title: Adv Cancer Res – volume: 137 start-page: 4358 year: 2015 end-page: 67 article-title: Development of a mitochondria‐targeted Hsp90 inhibitor based on the crystal structures of human TRAP1 publication-title: J Am Chem Soc – volume: 34 start-page: 60 year: 2015 end-page: 8 article-title: Assessing and maximizing data quality in macromolecular crystallography publication-title: Curr Opin Struct Biol – volume: 11 start-page: 1446 year: 2021 end-page: 68 article-title: The disruption of protein‐protein interactions with co‐chaperones and client substrates as a strategy towards Hsp90 inhibition publication-title: Acta Pharm Sin B – volume: 28 start-page: 235 year: 2000 end-page: 42 article-title: The Protein Data Bank publication-title: Nucleic Acids Res – volume: 27 start-page: 203 year: 2002 end-page: 8 article-title: Protein‐water interactions in a dynamic world publication-title: Trends Biochem Sci – volume: 64 start-page: 1545 year: 2021 end-page: 57 article-title: The development of Hsp90β‐selective inhibitors to overcome detriments associated with publication-title: J Med Chem – volume: 317 start-page: 61 year: 2012 end-page: 82 article-title: Hsp90 inhibitors and drugs from fragment and virtual screening publication-title: Top Curr Chem – volume: 117 start-page: 33204 year: 2020 end-page: 15 article-title: Assessment of enzyme active site positioning and tests of catalytic mechanisms through X‐ray‐derived conformational ensembles publication-title: Proc Natl Acad Sci U S A – volume: 112 start-page: 5039 year: 2015 end-page: 44 article-title: Homologous ligands accommodated by discrete conformations of a buried cavity publication-title: Proc Natl Acad Sci U S A – volume: 440 start-page: 1013 year: 2006 end-page: 7 article-title: Crystal structure of an Hsp90‐nucleotide‐p23/Sba1 closed chaperone complex publication-title: Nature – volume: 8 start-page: 2276 year: 2017 article-title: Protein conformational flexibility modulates kinetics and thermodynamics of drug binding publication-title: Nat Commun – volume: 141 start-page: 15818 year: 2019 end-page: 26 article-title: Water networks can determine the affinity of ligand binding to proteins publication-title: J Am Chem Soc – volume: 40 start-page: 117 year: 2015 end-page: 25 article-title: Hsp90 interaction with clients publication-title: Trends Biochem Sci – volume: 66 start-page: 125 year: 2010 end-page: 32 article-title: XDS publication-title: Acta Crystallogr D Biol Crystallogr – volume: 25 start-page: 1605 year: 2004 end-page: 12 article-title: UCSF chimera—A visualization system for exploratory research and analysis publication-title: J Comput Chem – volume: 388 start-page: 1033 year: 2009 end-page: 42 article-title: Different poses for ligand and chaperone in inhibitor‐bound Hsp90 and GRP94: implications for paralog‐specific drug design publication-title: J Mol Biol – volume: 4 start-page: 963 year: 2009 end-page: 6 article-title: Fragment‐based identification of Hsp90 inhibitors publication-title: ChemMedChem – volume: 9 start-page: 677 year: 2013 end-page: 84 article-title: Paralog‐selective Hsp90 inhibitors define tumor‐specific regulation of HER2 publication-title: Nat Chem Biol – ident: e_1_2_9_6_1 doi: 10.1002/cmdc.200900011 – ident: e_1_2_9_37_1 doi: 10.1039/D0SC04938G – ident: e_1_2_9_66_1 doi: 10.1073/pnas.2011350117 – ident: e_1_2_9_51_1 doi: 10.1021/acs.jmedchem.7b01608 – ident: e_1_2_9_33_1 doi: 10.1002/pro.423 – ident: e_1_2_9_38_1 doi: 10.1016/S0968-0004(02)02067-4 – ident: e_1_2_9_41_1 doi: 10.1021/acschembio.6b00747 – ident: e_1_2_9_31_1 doi: 10.1038/s41467-017-02013-1 – ident: e_1_2_9_24_1 doi: 10.1074/jbc.RA119.009960 – ident: e_1_2_9_45_1 doi: 10.1158/1078-0432.CCR-13-2571 – ident: e_1_2_9_54_1 doi: 10.1016/j.apsb.2020.11.015 – ident: e_1_2_9_12_1 doi: 10.1021/ja303477g – ident: e_1_2_9_50_1 doi: 10.1107/S0907444912044423 – ident: e_1_2_9_7_1 doi: 10.1093/nar/28.1.235 – ident: e_1_2_9_61_1 doi: 10.7554/eLife.74114 – ident: e_1_2_9_67_1 doi: 10.1016/j.ejmech.2022.114516 – ident: e_1_2_9_15_1 doi: 10.1016/j.bmcl.2013.11.036 – ident: e_1_2_9_34_1 doi: 10.1021/ja511893n – ident: e_1_2_9_8_1 doi: 10.1039/D1SC02751D – ident: e_1_2_9_10_1 doi: 10.1002/chem.201703398 – ident: e_1_2_9_58_1 doi: 10.1002/anie.202112919 – ident: e_1_2_9_48_1 doi: 10.1002/jcc.20084 – ident: e_1_2_9_16_1 doi: 10.1021/jm500042s – ident: e_1_2_9_4_1 doi: 10.1073/pnas.1703287114 – ident: e_1_2_9_19_1 doi: 10.1002/cbic.201500196 – ident: e_1_2_9_55_1 doi: 10.1074/jbc.M308661200 – ident: e_1_2_9_18_1 doi: 10.1124/mi.9.1.7 – ident: e_1_2_9_29_1 doi: 10.1016/j.tibs.2014.12.002 – ident: e_1_2_9_36_1 doi: 10.1107/S2059798319011471 – ident: e_1_2_9_59_1 doi: 10.2174/156802609789895737 – ident: e_1_2_9_2_1 doi: 10.1038/nature04716 – ident: e_1_2_9_13_1 doi: 10.7554/eLife.25235 – ident: e_1_2_9_57_1 doi: 10.1021/acs.jmedchem.2c00708 – ident: e_1_2_9_11_1 doi: 10.1021/jacs.9b06275 – ident: e_1_2_9_39_1 doi: 10.1107/S0021889807021206 – ident: e_1_2_9_21_1 doi: 10.2174/1568026616666160413141154 – ident: e_1_2_9_28_1 doi: 10.1107/S0907444909047337 – ident: e_1_2_9_25_1 doi: 10.1002/prot.25750 – ident: e_1_2_9_22_1 doi: 10.1038/nsmb.1565 – ident: e_1_2_9_5_1 doi: 10.1021/acschembio.5b00683 – ident: e_1_2_9_32_1 doi: 10.1007/978-3-030-40204-4_9 – ident: e_1_2_9_52_1 doi: 10.1007/128_2011_181 – ident: e_1_2_9_46_1 doi: 10.1016/S0076-6879(97)76066-X – ident: e_1_2_9_3_1 doi: 10.1038/s41467-017-02258-w – ident: e_1_2_9_35_1 doi: 10.1016/j.bbamcr.2011.09.003 – ident: e_1_2_9_40_1 doi: 10.1073/pnas.1500806112 – ident: e_1_2_9_63_1 doi: 10.1021/acs.jmedchem.8b00105 – ident: e_1_2_9_64_1 doi: 10.2174/1389450120666190829162544 – ident: e_1_2_9_65_1 doi: 10.1016/j.ejmech.2021.113604 – ident: e_1_2_9_14_1 doi: 10.1107/S0907444910007493 – ident: e_1_2_9_17_1 doi: 10.1017/S0033583520000128 – volume-title: NACCESS, computer program year: 1993 ident: e_1_2_9_23_1 – ident: e_1_2_9_30_1 doi: 10.1016/j.sbi.2015.07.003 – ident: e_1_2_9_47_1 doi: 10.1038/nchembio.1335 – ident: e_1_2_9_26_1 doi: 10.1021/jm060297x – ident: e_1_2_9_43_1 doi: 10.1021/acs.jmedchem.0c01700 – ident: e_1_2_9_53_1 doi: 10.1021/jm200350g – ident: e_1_2_9_60_1 doi: 10.1038/nrc2887 – ident: e_1_2_9_42_1 doi: 10.1002/anie.202015422 – ident: e_1_2_9_44_1 doi: 10.2174/138161213804143725 – ident: e_1_2_9_27_1 doi: 10.1016/j.jmb.2009.03.071 – ident: e_1_2_9_20_1 doi: 10.1016/bs.acr.2015.12.001 – ident: e_1_2_9_56_1 doi: 10.1021/acs.jmedchem.7b00057 – ident: e_1_2_9_62_1 doi: 10.1038/nrc1716 – ident: e_1_2_9_49_1 doi: 10.1021/acschembio.8b00443 – ident: e_1_2_9_9_1 doi: 10.1021/jm900357y
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Snippet	Isoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains...
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SubjectTerms	Antineoplastic Agents - chemistry Binding conformational flexibility Heat shock proteins HSP90 Heat-Shock Proteins - chemistry Hsp90 isoforms Hsp90 protein Humans Isoforms ligand binding Ligands pan‐Hsp90 inhibitors Protein Binding Protein Conformation Protein folding Protein Isoforms - chemistry Proteins Side effects Therapeutic targets water networks
Title	Pan‐HSP90 ligand binding reveals isoform‐specific differences in plasticity and water networks
URI	https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fpro.4629 https://www.ncbi.nlm.nih.gov/pubmed/36938943 https://www.proquest.com/docview/2806809534 https://www.proquest.com/docview/2788801055 https://pubmed.ncbi.nlm.nih.gov/PMC10108437
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