ArticlePloS one2015
Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Lipo-Glc-1,6-PIUBMB life · 2026Article
- Treatment of Single Patient With PMM2-Congenital Disorder of Glycosylation With Govorestat (AT-007), an Aldose Reductase Inhibitor.JIMD reports · 2025Article
- A comprehensive update of genotype-phenotype correlations in PMM2-CDG: insights from molecular and structural analyses.Orphanet journal of rare diseases · 2025Review
- Congenital disorders of glycosylation: narration of a story through its patents.Orphanet journal of rare diseases · 2023Review
- Tracer metabolomics reveals the role of aldose reductase in glycosylation.Cell reports. Medicine · 2023Article
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- Founder mutation in the PMM2 promotor causes hyperinsulinemic hypoglycaemia/polycystic kidney disease (HIPKD).Molecular genetics & genomic medicine · 2021Article
- Cystic kidney diseases associated with mutations in phosphomannomutase 2 promotor: a large spectrum of phenotypes.Pediatric nephrology (Berlin, Germany) · 2021Article
- Treatment Options in Congenital Disorders of Glycosylation.Frontiers in genetics · 2021Review
- Fatal outcome after heart surgery in PMM2-CDG due to a rare homozygous gene variant with double effects.Molecular genetics and metabolism reports · 2020Article
- Second-Generation Pharmacological Chaperones: Beyond Inhibitors.Molecules (Basel, Switzerland) · 2020Review
- Pharmacological Chaperones: A Therapeutic Approach for Diseases Caused by Destabilizing Missense Mutations.International journal of molecular sciences · 2020Review
- Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG.Disease models & mechanisms · 2019Article
- β-Glucose-1,6-Bisphosphate Stabilizes Pathological Phophomannomutase2 Mutants In Vitro and Represents a Lead Compound to Develop Pharmacological Chaperones for the Most Common Disorder of Glycosylation, PMM2-CDG.International journal of molecular sciences · 2019Article
- Yeast Models of Phosphomannomutase 2 Deficiency, a Congenital Disorder of Glycosylation.G3 (Bethesda, Md.) · 2019Article
- The Analysis of Variants in the General Population Reveals ThatInternational journal of molecular sciences · 2018Article
- CDG Therapies: From Bench to Bedside.International journal of molecular sciences · 2018Review
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- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The most frequent disorder of glycosylation is due to mutations in the gene encoding phosphomannomutase2 (PMM2-CDG). For this disease, which is autosomal and recessive, there is no cure at present. Most patients are composite heterozygous and carry one allele encoding an inactive mutant, R141H, and one encoding a hypomorphic mutant. Phosphomannomutase2 is a dimer. We reproduced composite heterozygosity in vitro by mixing R141H either with the wild type protein or the most common hypomorphic mutant F119L and compared the quaternary structure, the activity and the stability of the heterodimeric enzymes. We demonstrated that the activity of R141H/F119L heterodimers in vitro, which reproduces the protein found in patients, has the same activity of wild type/R141H, which reproduces the protein found in healthy carriers. On the other hand the stability of R141H/F119L appears to be reduced both in vitro and in vivo. These findings suggest that a therapy designed to enhance protein stability such as those based on pharmacological chaperones or modulation of proteostasis could be beneficial for PMM2-CDG patients carrying R141H/F119L genotype as well as for other genotypes where protein stability rather than specific activity is affected by mutations.
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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.