Structural Insights into Salinosporamide a Mediated Inhibition of the Human 20S Proteasome
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00618755" target="_blank" >RIV/61388963:_____/25:00618755 - isvavai.cz</a>
Alternative codes found
RIV/00216224:90127/25:00143937
Result on the web
<a href="https://doi.org/10.3390/molecules30061386" target="_blank" >https://doi.org/10.3390/molecules30061386</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/molecules30061386" target="_blank" >10.3390/molecules30061386</a>
Alternative languages
Result language
angličtina
Original language name
Structural Insights into Salinosporamide a Mediated Inhibition of the Human 20S Proteasome
Original language description
The 20S proteasome, a critical component of the ubiquitin-proteasome system, plays a central role in regulating protein degradation in eukaryotic cells. Marizomib (MZB), also known as salinosporamide A, is a natural gamma-lactam-beta-lactone compound derived from Salinispora tropica and is a potent 20S proteasome covalent inhibitor with demonstrated anticancer properties. Its broad-spectrum inhibition of all three proteasome subunits and its ability to cross the blood-brain barrier has made it a promising therapeutic candidate for glioblastoma. In addition to this, MZB also demonstrates significant inhibition against the 20S proteasome of Trichomonas vaginalis (Tv20S), a protozoan parasite, suggesting its potential for parasitic treatments. Here, we present the cryo-EM structure of the human 20S proteasome in complex with MZB at 2.55 & Aring, resolution. This structure reveals the binding mode of MZB to all six catalytic subunits within the two beta-rings of the 20S proteasome, providing a detailed molecular understanding of its irreversible inhibitory mechanism. These findings enhance the therapeutic potential of MZB for both cancer and parasitic diseases at the molecular level and highlight marine-derived natural products in targeting the proteasome for therapeutic applications.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecules
ISSN
1420-3049
e-ISSN
1420-3049
Volume of the periodical
30
Issue of the periodical within the volume
6
Country of publishing house
CH - SWITZERLAND
Number of pages
12
Pages from-to
1386
UT code for WoS article
001452896100001
EID of the result in the Scopus database
2-s2.0-105001140522