ArticleMolecular genetics & genomic medicine2014
Functional and structural impact of the most prevalent missense mutations in classic galactosemia.
Article in Molecular genetics & genomic medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 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
- Carbon source-dependent transcriptomic regulation and monosaccharide remodeling of exopolysaccharide biosynthesis in Pediococcus pceusentosa LL-07.BMC microbiology · 2025Article
- Classical Hereditary galactosemia: findings in patients and animal models.Metabolic brain disease · 2024Review
- Brain function in classic galactosemia, a galactosemia network (GalNet) members review.Frontiers in genetics · 2024Review
- Classic Galactosemia: Clinical and Computational Characterization of a NovelInternational journal of molecular sciences · 2023Review
- Novel mRNA therapy restores GALT protein and enzyme activity in a zebrafish model of classic galactosemia.Journal of inherited metabolic disease · 2022Article
- 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
- Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia.Orphanet journal of rare diseases · 2018Article
- Impaired fertility and motor function in a zebrafish model for classic galactosemia.Journal of inherited metabolic disease · 2018Article
- Sweet and sour: an update on classic galactosemia.Journal of inherited metabolic disease · 2017Review
- Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.Human molecular genetics · 2016Article
- Clinical profile and molecular characterization of Galactosemia in Brazil: identification of seven novel mutations.BMC medical genetics · 2016Article
- Arginine Functionally Improves Clinically Relevant Human Galactose-1-Phosphate Uridylyltransferase (GALT) Variants Expressed in a Prokaryotic Model.JIMD reports · 2015Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Galactose-1-phosphate uridylyltransferase (GALT) is a key enzyme in galactose metabolism, particularly important in the neonatal period due to ingestion of galactose-containing milk. GALT deficiency results in the genetic disorder classic galactosemia, whose pathophysiology is still not fully elucidated. Whereas classic galactosemia has been hypothesized to result from GALT misfolding, a thorough functional-structural characterization of GALT most prevalent variants was still lacking, hampering the development of alternative therapeutic approaches. The aim of this study was to investigate the structural-functional effects of nine GALT mutations, four of which account for the vast majority of the mutations identified in galactosemic patients. Several methodologies were employed to evaluate the mutations' impact on GALT function, on the protein secondary and tertiary structures, and on the aggregation propensity. The major structural effect concerns disturbed propensity for aggregation, particularly striking for the p.Q188R variant, resulting from the most frequent (∼60%) allele at a worldwide scale. The absence of major effects at the secondary and tertiary structure levels suggests that the disturbed aggregation results from subtle perturbations causing a higher and/or longer exposure of hydrophobic residues in the variants as compared to WT GALT. The results herein described indicate a possible benefit from introducing proteostasis regulators and/or chemical/pharmacological chaperones to prevent the accumulation of protein aggregates, in new avenues of therapeutic research for classic galactosemia.
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