ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structural and mechanistic insight into N-glycan processing by endo-α-mannosidase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 84 citations in OpenAlex.
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- Fluorinated Glycan Frameshifts: Automated Synthesis Expedites the Study of Glycan-Protein Interactions byAngewandte Chemie (International ed. in English) · 2026Article
- Catalyzing Carbohydrate Cleavage: Glycosidases and Their Mechanisms.Chemical reviews · 2026Review
- Structural and biochemical basis for activity of Aspergillus nidulans α-1,3-glucanases from glycoside hydrolase family 71.Communications biology · 2025Article
- New insights into the N-glycomes ofBBA advances · 2025Article
- Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution.bioRxiv : the preprint server for biology · 2024Article
- Evolution and phylogenetic distribution of endo-α-mannosidase.Glycobiology · 2023Article
- Self-recycling and partially conservative replication of mycobacterial methylmannose polysaccharides.Communications biology · 2023Article
- Unlocking the Hydrolytic Mechanism of GH92 α-1,2-Mannosidases: Computation Inspires the use of C-Glycosides as Michaelis Complex Mimics.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Host glycan utilization within the Bacteroidetes Sus-like paradigm.Glycobiology · 2021Article
- N-Glycan Biosynthesis: Basic Principles and Factors Affecting Its Outcome.Experientia supplementum (2012) · 2021Review
- Structure of human endo-α-1,2-mannosidase (MANEA), an antiviral host-glycosylation target.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A baculoviral system for the production of human β-glucocerebrosidase enables atomic resolution analysis.Acta crystallographica. Section D, Structural biology · 2020Article
- A Shut-and-Open Case: An Epoxide Intermediate Spotted in the Reaction Coordinate of a Family of Glycoside Hydrolases.ACS central science · 2020Article
- An Epoxide Intermediate in Glycosidase Catalysis.ACS central science · 2020Article
- Large-Scale Differential Gene Expression Transcriptomic Analysis Identifies a Metabolic Signature Shared by All Cancer Cells.Biomolecules · 2020Article
- Sulfated and sialylatedThe Journal of biological chemistry · 2020Article
- Genome-Wide Analysis of Whole Human Glycoside Hydrolases by Data-Driven Analysis in Silico.International journal of molecular sciences · 2019Article
- Spiro-epoxyglycosides as Activity-Based Probes for Glycoside Hydrolase Family 99 Endomannosidase/Endomannanase.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Exploration of Strategies for Mechanism-Based Inhibitor Design for Family GH99 endo-α-1,2-Mannanases.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
Abstract
N-linked glycans play key roles in protein folding, stability, and function. Biosynthetic modification of N-linked glycans, within the endoplasmic reticulum, features sequential trimming and readornment steps. One unusual enzyme, endo-α-mannosidase, cleaves mannoside linkages internally within an N-linked glycan chain, short circuiting the classical N-glycan biosynthetic pathway. Here, using two bacterial orthologs, we present the first structural and mechanistic dissection of endo-α-mannosidase. Structures solved at resolutions 1.7-2.1 Å reveal a (β/α)(8) barrel fold in which the catalytic center is present in a long substrate-binding groove, consistent with cleavage within the N-glycan chain. Enzymatic cleavage of authentic Glc(1/3)Man(9)GlcNAc(2) yields Glc(1/3)-Man. Using the bespoke substrate α-Glc-1,3-α-Man fluoride, the enzyme was shown to act with retention of anomeric configuration. Complexes with the established endo-α-mannosidase inhibitor α-Glc-1,3-deoxymannonojirimycin and a newly developed inhibitor, α-Glc-1,3-isofagomine, and with the reducing-end product α-1,2-mannobiose structurally define the -2 to +2 subsites of the enzyme. These structural and mechanistic data provide a foundation upon which to develop new enzyme inhibitors targeting the hijacking of N-glycan synthesis in viral disease and cancer.
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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.