ArticleNature communications2018
Molecular mechanism of a covalent allosteric inhibitor of SUMO E1 activating enzyme.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 70 citations in OpenAlex.
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- Immunomodulation of Pancreatic Cancer via Inhibition of SUMOylation and the CD155/TIGIT Pathway.Molecular cancer therapeutics · 2026Article
- Allosteric ensembles elucidate mechanisms of inhibition in the human soluble epoxide hydrolase.Communications biology · 2026Article
- Exon-skipping antisense oligonucleotides targeting SUMO1 and SUMO2 demonstrate chemosensitizing effects in NSCLC cells in tissue culture.Research square · 2026Article
- Cryo-EM structures of UBA6 reveal mechanisms of E1-E2 specificity and dual FAT10/ubiquitin thioester transfer.Nature communications · 2026Article
- Epoxy tetrahydrophthalimides as potential bioactive agents: synthesis and computational study.Pest management science · 2025Article
- Cryo-EM structures reveal the molecular mechanism of SUMO E1-E2 thioester transfer.Nature structural & molecular biology · 2025Article
- Targeting SUMOylation with Anacardic Acid Derivatives: Novel Insights into EGF Pathway Dysregulation in Cancer Using an In Silico Approach.ACS omega · 2025Article
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- The impact of dysregulation SUMOylation on prostate cancer.Journal of translational medicine · 2025Review
- SUMO Antibody Validation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- SUMOylation balance: a key determinant in synapse physiology.Frontiers in physiology · 2025Review
- The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.Biomedicines · 2024Review
- Targeted inhibition of SUMOylation: treatment of tumors.Human cell · 2024Review
- Article
- Exploring the Role of Unconventional Post-Translational Modifications in Cancer Diagnostics and Therapy.Current protein & peptide science · 2024Review
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- SUMOylation of RALY promotes vasculogenic mimicry in glioma cells via the FOXD1/DKK1 pathway.Cell biology and toxicology · 2023Article
- The SUMOylation and ubiquitination crosstalk in cancer.Journal of cancer research and clinical oncology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
E1 enzymes activate ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) in the first step of Ub/Ubl conjugation cascades and represent potential targets for therapeutic intervention in cancer and other life-threatening diseases. Here, we report the crystal structure of the E1 enzyme for the Ubl SUMO in complex with a recently discovered and highly specific covalent allosteric inhibitor (COH000). The structure reveals that COH000 targets a cryptic pocket distinct from the active site that is completely buried in all previous SUMO E1 structures and that COH000 binding to SUMO E1 is accompanied by a network of structural changes that altogether lock the enzyme in a previously unobserved inactive conformation. These structural changes include disassembly of the active site and a 180° rotation of the catalytic cysteine-containing SCCH domain, relative to conformational snapshots of SUMO E1 poised to catalyze adenylation. Altogether, our study provides a molecular basis for the inhibitory mechanism of COH000 and its SUMO E1 specificity, and also establishes a framework for potential development of molecules targeting E1 enzymes for other Ubls at a cryptic allosteric site.
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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.