ArticleHuman molecular genetics2016
Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pathophysiology and targets for treatment in hereditary galactosemia: A systematic review of animal and cellular models.Journal of inherited metabolic disease · 2020Pooled it
- Reshaping the Treatment Landscape of a Galactose Metabolism Disorder.Journal of inherited metabolic disease · 2025Review
- Improvement of Mutant Galactose-1-Phosphate Uridylyltransferase (GALT) Activity by FDA-Approved Pharmacochaperones: A Preliminary Study.International journal of molecular sciences · 2025Article
- Cytosolic UDP-Gal biosynthetic machinery is required for dimerization of SLC35A2 in the Golgi membrane and its interaction with B4GalT1.Frontiers in molecular biosciences · 2025Article
- Classic Galactosemia: Clinical and Computational Characterization of a NovelInternational journal of molecular sciences · 2023Review
- Molecular Mechanisms, Genotype-Phenotype Correlations and Patient-Specific Treatments in Inherited Metabolic Diseases.Journal of personalized medicine · 2023Article
- Molecular characterization of novel and rare DNA variants in patients with galactosemia.Frontiers in genetics · 2023Article
- Galactosemia: Biochemistry, Molecular Genetics, Newborn Screening, and Treatment.Biomolecules · 2022Review
- Simulation of the Interactions of Arginine with Wild-Type GALT Enzyme and the Classic Galactosemia-Related Mutant p.Q188R by a Computational Approach.Molecules (Basel, Switzerland) · 2021Article
- Analysis of the Structure-Function-Dynamics Relationships of GALT Enzyme and of Its Pathogenic Mutant p.Q188R: A Molecular Dynamics Simulation Study in Different Experimental Conditions.Molecules (Basel, Switzerland) · 2021Article
- Galactosemia: Towards Pharmacological Chaperones.Journal of personalized medicine · 2021Review
- Current and Future Treatments for Classic Galactosemia.Journal of personalized medicine · 2021Review
- Use of tandem affinity-buffer exchange chromatography online with native mass spectrometry for optimizing overexpression and purification of recombinant proteins.Methods in enzymology · 2021Article
- Naturally-Occurring Rare Mutations Cause Mild to Catastrophic Effects in the Multifunctional and Cancer-Associated NQO1 Protein.Journal of personalized medicine · 2020Article
- Discovery of Novel Inhibitors Targeting Multi-UDP-hexose Pyrophosphorylases as Anticancer Agents.Molecules (Basel, Switzerland) · 2020Article
- Screening for galactosemia: is there a place for it?International journal of general medicine · 2019Article
- Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia.Orphanet journal of rare diseases · 2018Article
- Sweet and sour: an update on classic galactosemia.Journal of inherited metabolic disease · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 Å resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore is a zbetter model for understanding the molecular consequences of disease mutations. Both uridylylation and zinc binding influence the stability and aggregation tendency of hGALT. This has implications for disease-associated variants where p.Gln188Arg, the most commonly detected, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate. As such our structure serves as a template in the future design of pharmacological chaperone therapies and opens new concepts about the roles of metal binding and activity in protein misfolding by disease-associated mutants.
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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.