Structural analysis of recombinant human ubiquitin-conjugating enzyme UbcH5c
- PMID: 28540177
- PMCID: PMC5430876
- DOI: 10.1016/j.apsb.2016.12.008
Structural analysis of recombinant human ubiquitin-conjugating enzyme UbcH5c
Abstract
UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α--triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22121 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.
Keywords: Crystal structure; Inflammatory target; NF-κB; UbcH5c; Ubiquitin-conjugating enzyme; Ubiquitination.
Figures






Similar articles
-
Discovery of Potent Small-Molecule Inhibitors of Ubiquitin-Conjugating Enzyme UbcH5c from α-Santonin Derivatives.J Med Chem. 2017 Aug 24;60(16):6828-6852. doi: 10.1021/acs.jmedchem.6b01829. Epub 2017 Aug 2. J Med Chem. 2017. PMID: 28696694
-
The E2 ubiquitin-conjugating enzyme UbcH5c: an emerging target in cancer and immune disorders.Drug Discov Today. 2020 Sep 16:S1359-6446(20)30369-X. doi: 10.1016/j.drudis.2020.09.015. Online ahead of print. Drug Discov Today. 2020. PMID: 32947046 Review.
-
Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis.Mol Cancer. 2022 Mar 10;21(1):70. doi: 10.1186/s12943-022-01538-4. Mol Cancer. 2022. PMID: 35272681 Free PMC article.
-
A sesquiterpene lactone from a medicinal herb inhibits proinflammatory activity of TNF-α by inhibiting ubiquitin-conjugating enzyme UbcH5.Chem Biol. 2014 Oct 23;21(10):1341-1350. doi: 10.1016/j.chembiol.2014.07.021. Epub 2014 Sep 4. Chem Biol. 2014. PMID: 25200604
-
Regulation of TNF-induced NF-κB activation by different cytoplasmic ubiquitination events.Cytokine Growth Factor Rev. 2011 Oct-Dec;22(5-6):277-86. doi: 10.1016/j.cytogfr.2011.11.002. Epub 2011 Nov 25. Cytokine Growth Factor Rev. 2011. PMID: 22119011 Review.
Cited by
-
Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168.Nat Chem Biol. 2025 May;21(5):668-680. doi: 10.1038/s41589-024-01750-x. Epub 2024 Oct 11. Nat Chem Biol. 2025. PMID: 39394267
-
Acetylation, Phosphorylation, Ubiquitination (Oh My!): Following Post-Translational Modifications on the Ubiquitin Road.Biomolecules. 2022 Mar 18;12(3):467. doi: 10.3390/biom12030467. Biomolecules. 2022. PMID: 35327659 Free PMC article. Review.
-
Structural basis of generic versus specific E2-RING E3 interactions in protein ubiquitination.Protein Sci. 2019 Oct;28(10):1758-1770. doi: 10.1002/pro.3690. Epub 2019 Aug 23. Protein Sci. 2019. PMID: 31340062 Free PMC article. Review.
-
Molecular Simulation Elaborating the Mechanism of 1β-Hydroxy Alantolactone Inhibiting Ubiquitin-Conjugating Enzyme UbcH5s.Sci Rep. 2020 Jan 10;10(1):141. doi: 10.1038/s41598-019-57104-4. Sci Rep. 2020. PMID: 31924820 Free PMC article.
-
Mechanisms of RNF168 nucleosome recognition and ubiquitylation.Mol Cell. 2024 Mar 7;84(5):839-853.e12. doi: 10.1016/j.molcel.2023.12.036. Epub 2024 Jan 18. Mol Cell. 2024. PMID: 38242129 Free PMC article.
References
-
- Chen G., Goeddel D.V. TNF-R1 signaling: a beautiful pathway. Science. 2002;296:1634–1635. - PubMed
-
- Bertrand M.J., Milutinovic S., Dickson K.M., Ho W.C., Boudreault A., Durkin J. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 2008;30:689–700. - PubMed
-
- Ea C.K., Deng L., Xia Z.P., Pineda G., Chen Z.J. Activation of IKK by TNFα requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO. Mol Cell. 2006;22:245–257. - PubMed
LinkOut - more resources
Full Text Sources
Other Literature Sources