ArticleProceedings of the National Academy of Sciences of the United States of America1996
Heterodimer formation and activity in the human enzyme galactose-1-phosphate uridylyltransferase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. 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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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 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
- Comparison of In Vitro and In Silico Assessments of Human Galactose-1-Phosphate Uridylyltransferase Coding Variants.Cureus · 2023Article
- Neonatal GALT gene replacement offers metabolic and phenotypic correction through early adulthood in a rat model of classic galactosemia.Journal of inherited metabolic disease · 2022Article
- A pilot study of neonatal GALT gene replacement using AAV9 dramatically lowers galactose metabolites in blood, liver, and brain and minimizes cataracts in GALT-null rat pups.Journal of inherited metabolic disease · 2021Article
- Cryptic residual GALT activity is a potential modifier of scholastic outcome in school age children with classic galactosemia.Journal of inherited metabolic disease · 2013Article
- Misfolding of galactose 1-phosphate uridylyltransferase can result in type I galactosemia.Biochimica et biophysica acta · 2013Article
- Galactose toxicity in animals.IUBMB life · 2009Review
- A yeast model reveals biochemical severity associated with each of three variant alleles of galactose-1P uridylyltransferase segregating in a single family.Journal of inherited metabolic disease · 2008Article
- Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.PLoS biology · 2006Article
- Improvement of galactose uptake in Saccharomyces cerevisiae through overexpression of phosphoglucomutase: example of transcript analysis as a tool in inverse metabolic engineering.Applied and environmental microbiology · 2005Article
- Studies of the V94M-substituted human UDPgalactose-4-epimerase enzyme associated with generalized epimerase-deficiency galactosaemia.Journal of inherited metabolic disease · 2000Article
- Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia.American journal of human genetics · 1999Article
- Characterization of two mutations associated with epimerase-deficiency galactosemia, by use of a yeast expression system for human UDP-galactose-4-epimerase.American journal of human genetics · 1997Article
- Biochemical characterization of the S135L allele of galactose-1-phosphate uridylyltransferase associated with galactosaemia.Journal of inherited metabolic disease · 1997Article
- A Drosophila melanogaster model of classic galactosemia.Disease models & mechanismsArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
One of the fundamental questions concerning expression and function of dimeric enzymes involves the impact of naturally occurring mutations on subunit assembly and heterodimer activity. This question is of particular interest for the human enzyme galactose-l-phosphate uridylyl-transferase (GALT), impairment of which results in the inherited metabolic disorder galactosemia, because many if not most patients studied to date are compound heterozygotes rather than true molecular homozygotes. Furthermore, the broad range of phenotypic severity observed in these patients raises the possibility that allelic combination, not just allelic constitution, may play some role in determining outcome. In the work described herein, we have selected two distinct naturally occurring null mutations of GALT, Q188R and R333W, and asked the questions (i) what are the impacts of these mutations on subunit assembly, and (ii) if heterodimers do form, are they active? To answer these questions, we have established a yeast system for the coexpression of epitope-tagged alleles of human GALT and investigated both the extent of specific GALT subunit interactions and the activity of defined heterodimer pools. We have found that both homodimers and heterodimers do form involving each of the mutant subunits tested and that both heterodimer pools retain substantial enzymatic activity. These results are significant not only in terms of their implications for furthering our understanding of galactosemia and GALT holoenzyme structure-function relationships but also because the system described may serve as a model for similar studies of other complexes composed of multiple subunits.
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