ArticleBiochemistry2013
Structural consequences of mutations to the α-tocopherol transfer protein associated with the neurodegenerative disease ataxia with vitamin E deficiency.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Enjoy Carefully: The Multifaceted Role of Vitamin E in Neuro-Nutrition.International journal of molecular sciences · 2021Review
- α-Tocopherol Stereoisomer Profiles in Matched Human Maternal and Umbilical Cord Plasma.Current developments in nutrition · 2021Article
- Tumorigenic p53 mutants undergo common structural disruptions including conversion to α-sheet structure.Protein science : a publication of the Protein Society · 2020Article
- Frailty, Cognitive Decline, Neurodegenerative Diseases and Nutrition Interventions.International journal of molecular sciences · 2019Review
- An in silico algorithm for identifying stabilizing pockets in proteins: test case, the Y220C mutant of the p53 tumor suppressor protein.Protein engineering, design & selection : PEDS · 2016Article
- Progressive ataxia due to alpha-tocopherol deficiency in Pakistan.Iranian journal of neurology · 2016Article
- Complexity of vitamin E metabolism.World journal of biological chemistry · 2016Review
- Mechanisms of recognition and binding of α-TTP to the plasma membrane by multi-scale molecular dynamics simulations.Frontiers in molecular biosciences · 2015Article
- DIVE: a data intensive visualization engine.Bioinformatics (Oxford, England) · 2014Article
- Analyzing disease-associated protein structures with visual analytics.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2013Article
- DIVE: a graph-based visual-analytics framework for big data.IEEE computer graphics and applicationsArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The α-tocopherol transfer protein (α-TTP) is a liver protein that transfers α-tocopherol (vitamin E) to very-low-density lipoproteins (VLDLs). These VLDLs are then circulated throughout the body to maintain blood α-tocopherol levels. Mutations to the α-TTP gene are associated with ataxia with vitamin E deficiency, a disease characterized by peripheral nerve degeneration. In this study, molecular dynamics simulations of the E141K and R59W disease-associated mutants were performed. The mutants displayed disruptions in and around the ligand-binding pocket. Structural analysis and ligand docking to the mutant structures predicted a decreased affinity for α-tocopherol. To determine the detailed mechanism of the mutation-related changes, we developed a new tool called ContactWalker that analyzes contact differences between mutant and wild-type proteins and highlights pathways of altered contacts within the mutant proteins. Taken together, our findings are in agreement with experiment and suggest structural explanations for the weakened ability of the mutants to bind and carry α-tocopherol.
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Registered trials
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