ArticleScientific reports2016
Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme in sialic acid biosynthesis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Preclinical assessment of GNEFuture science OA · 2026Article
- Article
- Quantitative analysis of inhibitor-induced assembly disruption in human UDP-GlcNAc 2-epimerase using mass photometry.Protein science : a publication of the Protein Society · 2025Article
- Expression of GNE mutant proteins increases CHO intracellular CMP-Neu5Ac levels without impact on bioprocess performance.Bioprocess and biosystems engineering · 2025Article
- [Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Review
- Insights into structure and activity of a UDP-GlcNAc 2-epimerase involved in secondary cell wall polymer biosynthesis inFrontiers in molecular biosciences · 2024Article
- Role of Non-Coding RNAs in Hepatocellular Carcinoma Progression: From Classic to Novel Clinicopathogenetic Implications.Cancers · 2023Review
- Real-time monitoring of the sialic acid biosynthesis pathway by NMR.Chemical science · 2023Article
- Glycation Interferes with the Activity of the Bi-Functional UDP-Biomolecules · 2023Article
- Regulation of angiotensin-converting enzyme 2 isoforms by type 2 inflammation and viral infection in human airway epithelium.Mucosal immunology · 2023Article
- Multidimensional analyses of the pathomechanism caused by the non-catalytic GNE variant, c.620A>T, in patients with GNE myopathy.Scientific reports · 2022Article
- Dynamic tracing of sugar metabolism reveals the mechanisms of action of synthetic sugar analogs.Glycobiology · 2022Article
- Generation and Characterization of a Skeletal Muscle Cell-Based Model Carrying One Single Gne Allele: Implications in Actin Dynamics.Molecular neurobiology · 2021Article
- N-acetylmannosamine-6-phosphate 2-epimerase uses a novel substrate-assisted mechanism to catalyze amino sugar epimerization.The Journal of biological chemistry · 2021Article
- Racemases and epimerases operating through a 1,1-proton transfer mechanism: reactivity, mechanism and inhibition.Chemical Society reviews · 2021Review
- Metabolic Glycoengineering in hMSC-TERT as a Model for Skeletal Precursors by Using Modified Azide/Alkyne Monosaccharides.International journal of molecular sciences · 2021Article
- Severe Congenital Thrombocytopenia Characterized by Decreased Platelet Sialylation and Moderate Complement Activation Caused by Novel Compound Heterozygous Variants inFrontiers in immunology · 2021Article
- Sialuria: Ninth Patient Described Has a Novel Mutation in GNE.JIMD reports · 2019Article
- The Many Ways by WhichMolecules (Basel, Switzerland) · 2018Review
- GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production. It is different from the non-hydrolyzing enzymes for bacterial cell wall biosynthesis, and it is feed-back inhibited by the downstream product CMP-Neu5Ac. Here the complex crystal structure of the N-terminal epimerase part of human GNE shows a tetramer in which UDP binds to the active site and CMP-Neu5Ac binds to the dimer-dimer interface. The enzyme is locked in a tightly closed conformation. By comparing the UDP-binding modes of the non-hydrolyzing and hydrolyzing UDP-GlcNAc epimerases, we propose a possible explanation for the mechanistic difference. While the epimerization reactions of both enzymes are similar, Arg113 and Ser302 of GNE are likely involved in product hydrolysis. On the other hand, the CMP-Neu5Ac binding mode clearly elucidates why mutations in Arg263 and Arg266 can cause sialuria. Moreover, full-length modelling suggests a channel for ManNAc trafficking within the bifunctional enzyme.
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