On the Origin of the Different Reversible Characters of Salinosporamide A and Homosalinosporamide A in the Covalent Inhibition of the Human 20S Proteasome

ACS Catalysis ◽  
2021 ◽  
Vol 11 (18) ◽  
pp. 11806-11819
Author(s):  
Natalia Serrano-Aparicio ◽  
Vicent Moliner ◽  
Katarzyna Świderek
Keyword(s):  
20S Proteasome ◽  
Salinosporamide A ◽  
Covalent Inhibition

Synthesis of Salinosporamide A and Its Analogs as 20S Proteasome Inhibitors and SAR Summarization

2011 ◽  
Vol 11 (23) ◽  
pp. 2906-2922 ◽  
Author(s):  
Yuheng Ma ◽  
Lili Qu ◽  
Zhenming Liu ◽  
Liangren Zhang ◽  
Zhenjun Yang ◽  
...  
Keyword(s):  
Proteasome Inhibitors ◽  
20S Proteasome ◽  
Salinosporamide A

1,2,4-Oxadiazoles Identified by Virtual Screening and their Non-Covalent Inhibition of the Human 20S Proteasome

2013 ◽  
Vol 20 (18) ◽  
pp. 2351-2362 ◽  
Author(s):  
X. Maréchal ◽  
E. Genin ◽  
L. Qin ◽  
O. Sperandio ◽  
M. Montes ◽  
...  
Keyword(s):  
Virtual Screening ◽  
20S Proteasome ◽  
Covalent Inhibition

Nature of Irreversible Inhibition of Human 20S Proteasome by Salinosporamide A. The Critical Role of Lys–Asp Dyad Revealed from Electrostatic Effects Analysis

ACS Catalysis ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 3575-3589
Author(s):  
Natalia Serrano-Aparicio ◽  
Vicent Moliner ◽  
Katarzyna Świderek
Keyword(s):  
Critical Role ◽  
20S Proteasome ◽  
Electrostatic Effects ◽  
Irreversible Inhibition ◽  
Salinosporamide A

Indium-catalyzed Conia-ene reaction for alkaloid synthesis

2009 ◽  
Vol 81 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Susumi Hatakeyama
Keyword(s):  
Proteasome Inhibitor ◽  
20S Proteasome ◽  
Ene Reaction ◽  
Excellent Yield ◽  
Salinosporamide A ◽  
Alkaloid Synthesis ◽  
Synthetic Utility ◽  
Reaction Proceeds

In(OTf)3-catalyzed cyclization of nitrogen- and oxygen-tethered acetylenic malonic esters provides various five- to seven-membered heterocycles in moderate to excellent yield, and the reaction proceeds with no racemization and complete E-selectivity in the case of chiral and nonterminal alkynes. The synthetic utility is demonstrated by the synthesis of (-)-salinosporamide A, a highly potent 20S proteasome inhibitor, and (+)-neooxazolomycin, a member of the oxazolomycin family of antibiotics.

1,2,4-Oxadiazoles Identified by Virtual Screening and their Non-Covalent Inhibition of the Human 20S Proteasome

2013 ◽  
Vol 888 (888) ◽  
pp. 1-12
Author(s):  
X. Marechal ◽  
E. Genin ◽  
L. Qin ◽  
O. Sperandio ◽  
M. Montes ◽  
...  
Keyword(s):  
Virtual Screening ◽  
20S Proteasome ◽  
Covalent Inhibition

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

2020 ◽  
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
Boronic Acid ◽  
Computational Study ◽  
Ubiquitin Proteasome System ◽  
Bayesian Optimization ◽  
Inhibition Mechanism ◽  
20S Proteasome ◽  
Acid Base ◽  
Ubiquitin Proteasome ◽  
Infection Cycles

The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

20S Proteasome complex

2007 ◽  
Author(s):  
Keyword(s):  
20S Proteasome
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