ArticleThe Journal of biological chemistry2011
Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase-deficient fibroblasts.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Fructose 1-phosphate inhibits mannose phosphate isomerase to suppress hepatocellular carcinogenesis.Signal transduction and targeted therapy · 2026Article
- Drug repurposing: antimicrobial and antibiofilm effects of MLS0315771 against Gram-positive bacteria.BMC microbiology · 2026Article
- Targeted metabolomic evaluation of peripheral blood mononucleated cells from patients with PMM2-CDG.Scientific reports · 2025Article
- AAV-based gene replacement therapy prevents and halts manifestation of abnormal neurological phenotypes in a novel mouse model of PMM2-CDG.Gene therapy · 2025Article
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- AAV9-basedMolecular genetics and metabolism reports · 2024Article
- Glycolytic interference blocks influenza A virus propagation by impairing viral polymerase-driven synthesis of genomic vRNA.PLoS pathogens · 2023Article
- Mannose metabolism inhibition sensitizes acute myeloid leukaemia cells to therapy by driving ferroptotic cell death.Nature communications · 2023Article
- Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia.Cancer science · 2021Article
- Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG).Orphanet journal of rare diseases · 2020Article
- 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
- CDG Therapies: From Bench to Bedside.International journal of molecular sciences · 2018Review
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- Article
- A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2.Human molecular genetics · 2016Article
- Synaptic roles for phosphomannomutase type 2 in a new Drosophila congenital disorder of glycosylation disease model.Disease models & mechanisms · 2016Article
- Conformational response to ligand binding in phosphomannomutase2: insights into inborn glycosylation disorder.The Journal of biological chemistry · 2014Article
- Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1.Bioorganic & medicinal chemistry letters · 2014Article
- Congenital disorders of glycosylation with neonatal presentation.BMJ case reports · 2014Article
Corrections and comments
- Erratum issuedScott, David A [added]
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Congenital disorders of glycosylation (CDG) are rare genetic disorders due to impaired glycosylation. The patients with subtypes CDG-Ia and CDG-Ib have mutations in the genes encoding phosphomannomutase 2 (PMM2) and phosphomannose isomerase (MPI or PMI), respectively. PMM2 (mannose 6-phosphate → mannose 1-phosphate) and MPI (mannose 6-phosphate ⇔ fructose 6-phosphate) deficiencies reduce the metabolic flux of mannose 6-phosphate (Man-6-P) into glycosylation, resulting in unoccupied N-glycosylation sites. Both PMM2 and MPI compete for the same substrate, Man-6-P. Daily mannose doses reverse most of the symptoms of MPI-deficient CDG-Ib patients. However, CDG-Ia patients do not benefit from mannose supplementation because >95% Man-6-P is catabolized by MPI. We hypothesized that inhibiting MPI enzymatic activity would provide more Man-6-P for glycosylation and possibly benefit CDG-Ia patients with residual PMM2 activity. Here we show that MLS0315771, a potent MPI inhibitor from the benzoisothiazolone series, diverts Man-6-P toward glycosylation in various cell lines including fibroblasts from CDG-Ia patients and improves N-glycosylation. Finally, we show that MLS0315771 increases mannose metabolic flux toward glycosylation in zebrafish embryos.
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Registered trials
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.