ArticleProteins2019
Structures of Hsp90α and Hsp90β bound to a purine-scaffold inhibitor reveal an exploitable residue for drug selectivity.
Article in Proteins, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 11 citations in OpenAlex.
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- Inherent MS-cleavability of diazirine photo-cross-links enables residue-level structural analysis.Nature communications · 2026Article
- Network Pharmacology and Molecular Docking-Based Investigation of Empagliflozin's Therapeutic Potential in Chronic Kidney Disease.Life (Basel, Switzerland) · 2026Article
- Heat shock protein Gp96 (Grp94) in malaria: functional insights at the host-parasite interface and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Article
- Absolute and Relative Binding Free Energy Calculations of Nucleotides to Multiple Protein Classes.Journal of chemical theory and computation · 2025Article
- Phosphorylation-Driven Epichaperome Assembly: A Critical Regulator of Cellular Adaptability and Proliferation.Research square · 2024Article
- Pan-HSP90 ligand binding reveals isoform-specific differences in plasticity and water networks.Protein science : a publication of the Protein Society · 2023Article
- Network pharmacology and experimental validation to reveal the target of matrine against PRRSV.iScience · 2023Article
- Protection against Aβ-induced neuronal damage by KU-32: PDHK1 inhibition as important target.Frontiers in aging neuroscience · 2023Article
- Multiplex Immunostaining Method to Distinguish HSP Isoforms in Cancer Tissue Specimens.Methods in molecular biology (Clifton, N.J.) · 2023Article
- HSP70 and HSP90 in Cancer: Cytosolic, Endoplasmic Reticulum and Mitochondrial Chaperones of Tumorigenesis.Frontiers in oncology · 2022Review
- Chemistry, Biosynthesis, Physicochemical and Biological Properties of Rubiadin: A Promising Natural Anthraquinone for New Drug Discovery and Development.Drug design, development and therapy · 2021Review
- NECA derivatives exploit the paralog-specific properties of the site 3 side pocket of Grp94, the endoplasmic reticulum Hsp90.The Journal of biological chemistry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hsp90α and Hsp90β are implicated in a number of cancers and neurodegenerative disorders but the lack of selective pharmacological probes confounds efforts to identify their individual roles. Here, we analyzed the binding of an Hsp90α-selective PU compound, PU-11-trans, to the two cytosolic paralogs. We determined the co-crystal structures of Hsp90α and Hsp90β bound to PU-11-trans, as well as the structure of the apo Hsp90β NTD. The two inhibitor-bound structures reveal that Ser52, a nonconserved residue in the ATP binding pocket in Hsp90α, provides additional stability to PU-11-trans through a water-mediated hydrogen-bonding network. Mutation of Ser52 to alanine, as found in Hsp90β, alters the dissociation constant of Hsp90α for PU-11-trans to match that of Hsp90β. Our results provide a structural explanation for the binding preference of PU inhibitors for Hsp90α and demonstrate that the single nonconserved residue in the ATP-binding pocket may be exploited for α/β selectivity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.