ArticleMolecular genetics & genomic medicine2013
Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation.
Article in Molecular genetics & genomic medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Congenital disorders of glycosylation: narration of a story through its patents.Orphanet journal of rare diseases · 2023Review
- Cysteine Pathogenic Variants of PMM2 Are Sensitive to Environmental Stress with Loss of Structural Stability.Oxidative medicine and cellular longevity · 2023Article
- 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
- 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
- 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
- Article
- A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2.Human molecular genetics · 2016Article
- On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry.Journal of the American Chemical Society · 2016Article
- Article
- Looking for protein stabilizing drugs with thermal shift assay.Drug testing and analysis · 2015Article
- Heterodimerization of Two Pathological Mutants Enhances the Activity of Human Phosphomannomutase2.PloS one · 2015Article
- Conformational response to ligand binding in phosphomannomutase2: insights into inborn glycosylation disorder.The Journal of biological chemistry · 2014Article
- Mannose metabolism: more than meets the eye.Biochemical and biophysical research communications · 2014Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphomannomutase 2 (PMM2) deficiency represents the most frequent type of congenital disorders of glycosylation. For this disease there is no cure at present. The complete loss of phosphomannomutase activity is probably not compatible with life and people affected carry at least one allele with residual activity. We characterized wild-type PMM2 and its most common hypomorphic mutant, p.F119L, which is associated with a severe phenotype of the disease. We demonstrated that active species is the dimeric enzyme and that the mutation weakens the quaternary structure and, at the same time, affects the activity and the stability of the enzyme. We demonstrated that ligand binding stabilizes both proteins, wild-type and F119L-PMM2, and promotes subunit association in vitro. The strongest effects are observed with glucose-1,6-bisphosphate (Glc-1,6-P2) or with monophosphate glucose in the presence of vanadate. This finding offers a new approach for the treatment of PMM2 deficiency. We propose to enhance Glc-1,6-P2 concentration either acting on the metabolic pathways that control its synthesis and degradation or exploiting prodrugs that are able to cross membranes.
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