ArticleHuman mutation2010
Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type.
Article in Human mutation, 2010. 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, 26 citations in OpenAlex.
- Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin BCell reports. Medicine · 2022Pooled it
- Propionate metabolism is dysregulated in non-small cell lung cancer patients and EGFR-mutant drug-tolerant persister cells.Scientific reports · 2026Article
- Propionate metabolism dysregulation promotes drug-tolerant persister cell survival in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2025Article
- Identifying and predicting the pathogenic effects of a novel variant inducing severe early onset MMA: a bioinformatics approach.Hereditas · 2023Article
- Identification of Novel Mutations in the MMAA and MUT Genes among Methylmalonic Aciduria Families.Iranian biomedical journal · 2023Article
- Tumor-produced and aging-associated oncometabolite methylmalonic acid promotes cancer-associated fibroblast activation to drive metastatic progression.Nature communications · 2022Article
- Spectrum and characterization of bi-allelic variants in MMAB causing cblB-type methylmalonic aciduria.Human genetics · 2022Article
- Genetic testing is necessary for correct diagnosis and treatment in patients with isolated methylmalonic aciduria: a case report.BMC pediatrics · 2021Article
- Clinical and molecular findings in 37 Turkish patients with isolated methylmalonic acidemiaTurkish journal of medical sciences · 2021Article
- Second-Generation Pharmacological Chaperones: Beyond Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Mutation analysis of genes related to methylmalonic acidemia: identification of eight novel mutations.Molecular biology reports · 2019Article
- Autozygosity mapping of methylmalonic acidemia associated genes by short tandem repeat markers facilitates the identification of five novel mutations in an Iranian patient cohort.Metabolic brain disease · 2018Article
- Spectroscopic Studies of the EutT Adenosyltransferase from Salmonella enterica: Mechanism of Four-Coordinate Co(II)Cbl Formation.Journal of the American Chemical Society · 2016Article
- Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies.Clinical genetics · 2015Article
- Spectroscopic studies of the Salmonella enterica adenosyltransferase enzyme SeCobA: molecular-level insight into the mechanism of substrate Cob(II)alamin activation.Biochemistry · 2014Article
- Innovative strategies to treat protein misfolding in inborn errors of metabolism: pharmacological chaperones and proteostasis regulators.Journal of inherited metabolic disease · 2014Review
- Pharmacological chaperones as a potential therapeutic option in methylmalonic aciduria cblB type.Human molecular genetics · 2013Article
- Loss of allostery and coenzyme B12 delivery by a pathogenic mutation in adenosyltransferase.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
atpcob(I)alamin adenosyltransferase (ATR, E.C.2.5.1.17) converts reduced cob(I)alamin to the adenosylcobalamin cofactor. Mutations in the MMAB gene encoding ATR are responsible for the cblB type methylmalonic aciduria. Here we report the functional analysis of five cblB mutations to determine the underlying molecular basis of the dysfunction. The transcriptional profile along with minigenes analysis revealed that c.584G>A, c.349-1G>C, and c.290G>A affect the splicing process. Wild-type ATR and the p.I96T (c.287T>C) and p.R191W (c.571C>T) mutant proteins were expressed in a prokaryote and a eukaryotic expression systems. The p.I96T protein was enzymatically active with a K(M) for ATP and K(D) for cob(I)alamin similar to wild-type enzyme, but exhibited a 40% reduction in specific activity. Both p.I96T and p.R191W mutant proteins are less stable than the wild-type protein, with increased stability when expressed under permissive folding conditions. Analysis of the oligomeric state of both mutants showed a structural defect for p.I96T and also a significant impact on the amount of recovered mutant protein that was more pronounced for p.R191W that, along with the structural analysis, suggest they might be misfolded. These results could serve as a basis for the implementation of pharmacological therapies aimed at increasing the residual activity of this type of mutations.
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