ArticleProceedings of the National Academy of Sciences of the United States of America2013
Structural snapshots illustrate the catalytic cycle of β-galactocerebrosidase, the defective enzyme in Krabbe disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- GALC variants affect galactosylceramidase enzymatic activity and risk of Parkinson's disease.Brain : a journal of neurology · 2023Pooled it
- Catalyzing Carbohydrate Cleavage: Glycosidases and Their Mechanisms.Chemical reviews · 2026Review
- Molecular Dynamics Simulations of 4Computational and structural biotechnology journal · 2026Article
- Abnormal Splicing ofBiomedicines · 2025Article
- Molecular Characterization of the GALC Mutation Thr112Ala Causing Krabbe Disease.International journal of molecular sciences · 2025Article
- Structure and function of a β-1,2-galactosidase from Bacteroides xylanisolvens, an intestinal bacterium.Communications biology · 2025Article
- Impact of an irreversible β-galactosylceramidase inhibitor on the lipid profile of zebrafish embryos.Computational and structural biotechnology journal · 2024Article
- Late-onset Krabbe disease presenting as spastic paraplegia - implications of GCase and CTSB/D.Annals of clinical and translational neurology · 2024Article
- In silico modelling of the function of disease-related CAZymes.Essays in biochemistry · 2023Article
- Altered plasma membrane abundance of the sulfatide-binding protein NF155 links glycosphingolipid imbalances to demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- β-Galactosylceramidase Deficiency Causes Upregulation of Long Pentraxin-3 in the Central Nervous System of Krabbe Patients andInternational journal of molecular sciences · 2022Article
- The Immunogenetics of Autoimmune Blistering Diseases.Advances in experimental medicine and biology · 2022Review
- Fluorimetric assay with a novel substrate for quantification of galactocerebrosidase activity in dried blood spot specimens.Practical laboratory medicine · 2020Article
- X-Ray Crystallography in Structure-Function Characterization of Therapeutic Enzymes.Advances in experimental medicine and biology · 2019Review
- Distinguishing the differences in β-glycosylceramidase folds, dynamics, and actions informs therapeutic uses.Journal of lipid research · 2018Article
- The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure.Nature communications · 2018Article
- Epithelial-mesenchymal transition and GALC expression of circulating tumor cells indicate metastasis and poor prognosis in non-small cell lung cancer.Cancer biomarkers : section A of Disease markers · 2018Article
- Contribution of Shape and Charge to the Inhibition of a Family GH99 endo-α-1,2-Mannanase.Journal of the American Chemical Society · 2017Article
- New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones.Journal of neuroscience research · 2016Review
- Biochemical, cell biological, pathological, and therapeutic aspects of Krabbe's disease.Journal of neuroscience research · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glycosphingolipids are ubiquitous components of mammalian cell membranes, and defects in their catabolism by lysosomal enzymes cause a diverse array of diseases. Deficiencies in the enzyme β-galactocerebrosidase (GALC) cause Krabbe disease, a devastating genetic disorder characterized by widespread demyelination and rapid, fatal neurodegeneration. Here, we present a series of high-resolution crystal structures that illustrate key steps in the catalytic cycle of GALC. We have captured a snapshot of the short-lived enzyme-substrate complex illustrating how wild-type GALC binds a bona fide substrate. We have extensively characterized the enzyme kinetics of GALC with this substrate and shown that the enzyme is active in crystallo by determining the structure of the enzyme-product complex following extended soaking of the crystals with this same substrate. We have also determined the structure of a covalent intermediate that, together with the enzyme-substrate and enzyme-product complexes, reveals conformational changes accompanying the catalytic steps and provides key mechanistic insights, laying the foundation for future design of pharmacological chaperones.
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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.