ArticleThe Journal of biological chemistry2018
Crystal structure of a human ubiquitin E1-ubiquitin complex reveals conserved functional elements essential for activity.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Identification of the first peptide inhibitor of UBE2C enzymatic activity: insights from metadynamics-guided folding and binding studies.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- UBE2C at the crossroads of cell cycle regulation and DNA damage response in cancer.Cell biology and toxicology · 2026Review
- Quercetin, a flavonoid, suppresses viral proliferation by interfering with the ubiquitin transfer from E1 to E2 enzymes.PLoS pathogens · 2026Article
- Cryo-EM structures of UBA6 reveal mechanisms of E1-E2 specificity and dual FAT10/ubiquitin thioester transfer.Nature communications · 2026Article
- SHPRH together with the Ube2D family of enzymes directly ubiquitinates PCNA at Lys164 in vitro.PloS one · 2026Article
- UBA1 as a proteostasis-innate immunity checkpoint: lessons from vexas syndrome and therapeutic implications.Frontiers in immunology · 2026Review
- Cryo-EM structures reveal the molecular mechanism of SUMO E1-E2 thioester transfer.Nature structural & molecular biology · 2025Article
- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- The Two Tomato Ubiquitin E1 Enzymes Play Unequal Roles in Host Immunity.Molecular plant pathology · 2025Article
- Molecular choreography of E1 enzymes in ubiquitin-like protein cascades: New insights into dynamics and specificity.The Journal of biological chemistry · 2025Review
- E2-Ub-R74G strategy reveals E2-specific ubiquitin conjugation profiles in live cells.Nature chemical biology · 2025Article
- Lycorine hydrochloride directly targets UBA1 to suppress cellular senescence.Acta pharmaceutica Sinica. B · 2025Article
- A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.PLoS pathogens · 2024Article
- Shared and distinct mechanisms of UBA1 inactivation across different diseases.The EMBO journal · 2024Article
- Sensitivity to targeted UBA1 inhibition in a myeloid cell line model of VEXAS syndrome.Blood advances · 2023Article
- Cell-Permeable Stimuli-Responsive Ubiquitin Probe for Time-Resolved Monitoring of Substrate Ubiquitination in Live Cells.JACS Au · 2023Article
- Unraveling the Mechanism of Action of Myricetin in the Inhibition of hUba1∼Ubiquitin Thioester Bond Formation viaACS omega · 2023Article
- Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes.Nature communications · 2023Article
- Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer.Nature communications · 2023Article
- Involvement in Fertilization and Expression of Gamete Ubiquitin-Activating Enzymes UBA1 and UBA6 in the AscidianInternational journal of molecular sciences · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Ubiquitin (Ub) signaling plays a key regulatory role in nearly every aspect of eukaryotic biology and is initiated by E1 enzymes that activate and transfer Ub to E2 Ub-conjugating enzymes. Despite Ub E1's fundamental importance to the cell and its attractiveness as a target for therapeutic intervention in cancer and other diseases, its only available structural information is derived from yeast orthologs of human ubiquitin-like modifier-activating enzyme 1 (hUBA1). To illuminate structural differences between yeast and hUBA1 structures that might be exploited for the development of small-molecule therapeutics, we determined the first crystal structure of a hUBA1-Ub complex. Using structural analysis, molecular modeling, and biochemical analysis, we demonstrate that hUBA1 shares a conserved overall structure and mechanism with previously characterized yeast orthologs, but displays subtle structural differences, particularly within the active site. Computational analysis revealed four potential ligand-binding hot spots on the surface of hUBA1 that might serve as targets to inhibit hUBA1 at the level of Ub activation or E2 recruitment or that might potentially be used in approaches such as protein-targeting chimeric molecules. Taken together, our work enhances our understanding of the hUBA1 mechanism, provides an improved framework for the development of small-molecule inhibitors of UBA1, and serves as a stepping stone for structural studies that involve the enzymes of the human Ub system at the level of both E1 and E2.
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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.