ArticlePloS one2016
Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations.International journal of molecular sciences · 2016Pooled it
- Genotype-Phenotype Correlations in 293 Russian Patients with Causal Fabry Disease Variants.Genes · 2023Article
- Pharmacological Chaperones and Protein Conformational Diseases: Approaches of Computational Structural Biology.International journal of molecular sciences · 2023Review
- Enzyme Replacement Therapy for FABRY Disease: Possible Strategies to Improve Its Efficacy.International journal of molecular sciences · 2023Article
- Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease.International journal of molecular sciences · 2023Article
- Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones.International journal of molecular sciences · 2022Article
- Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease.International journal of molecular sciences · 2021Review
- Fabry Disease: Molecular Basis, Pathophysiology, Diagnostics and Potential Therapeutic Directions.Biomolecules · 2021Review
- Second-Generation Pharmacological Chaperones: Beyond Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- β-Glucose-1,6-Bisphosphate Stabilizes Pathological Phophomannomutase2 Mutants In Vitro and Represents a Lead Compound to Develop Pharmacological Chaperones for the Most Common Disorder of Glycosylation, PMM2-CDG.International journal of molecular sciences · 2019Article
- Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.BMC bioinformatics · 2018Article
- Lysosomal storage diseases.Nature reviews. Disease primers · 2018Review
- Emptying the stores: lysosomal diseases and therapeutic strategies.Nature reviews. Drug discovery · 2018Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay.
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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.