Crystal Structure of Epoxomicin:20S Proteasome Reveals a Molecular Basis for Selectivity of α‘,β‘-Epoxyketone Proteasome Inhibitors
Abstract
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCrystal Structure of Epoxomicin:20S Proteasome Reveals a Molecular Basis for Selectivity of α',β'-Epoxyketone Proteasome InhibitorsMichael Groll, Kyung Bo Kim, Norman Kairies, Robert Huber, and Craig M. CrewsView Author Information Max Planck Institut für Biochemie D-82152 Martinsried, Germany Departments of Molecular, Cellular, and Developmental Biology and Pharmacology, Yale University 219 Prospect Street, New Haven, Connecticut 06520-8103 Cite this: J. Am. Chem. Soc. 2000, 122, 6, 1237–1238Publication Date (Web):January 28, 2000Publication History Received6 October 1999Published online28 January 2000Published inissue 1 February 2000https://pubs.acs.org/doi/10.1021/ja993588mhttps://doi.org/10.1021/ja993588mrapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views3045Altmetric-Citations274LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Adducts,Chemical specificity,Crystal structure,Inhibitors,Peptides and proteins Get e-Alerts
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These nucleophilic centers are also present in DNA and other biologically relevant compounds, such as glutathione.
“These nucleophilic centers are also present in DNA and other biologically relevant compounds, such as glutathione.116–121”
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The epoxyketone moiety in carfilzomib forms a morpholino ring with the catalytic N-terminal threonine of the 20S proteasome.
“The epoxyketone moiety in carfilzomib forms a morpholino ring with the catalytic N-terminal threonine of the 20S proteasome”
From Advances in covalent drug discovery (2022) · cites this paper as [127]
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- Authors
- Groll, M., Kim, K. B., Kairies, N., Huber, R., & Crews, C. M.
- Affiliations
- Yale University (US)
- Corresponding author
- Crews, Craig M.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2000-01-28
- Volume
- 122
- Issue
- 6
- Pages
- 1237-1238
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W4235721540
- Cited by
- 304
- References
- 16
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 3 · 2021: 12 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 16 · 2016: 13 · 2015: 19 · 2014: 24 · 2013: 24 · 2012: 21
- FWCI
- 3.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Chemical Society (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- epoxomicin, 20S proteasome, proteasome inhibitors, inhibitor selectivity, crystal structure, ubiquitin-proteasome system, structure-based design
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