Computational Study of Glycerol Binding within the Active Site of Coenzyme B12-Dependent Diol Dehydratase

2019 ◽  
Vol 123 (29) ◽  
pp. 6178-6187 ◽  
Author(s):  
Luka Bilić ◽  
Danijela Barić ◽  
Radha Dilip Banhatti ◽  
David M. Smith ◽  
Borislav Kovačević
Keyword(s):  
Active Site ◽  
Computational Study ◽  
Coenzyme B12 ◽  
Diol Dehydratase

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.

Identification of the active site of human mitochondrial malonyl-coenzyme a decarboxylase: A combined computational study

2016 ◽  
Vol 84 (6) ◽  
pp. 792-802 ◽  
Author(s):  
Baoping Ling ◽  
Yuxia Liu ◽  
Xiaoping Li ◽  
Zhiguo Wang ◽  
Siwei Bi
Keyword(s):  
Active Site ◽  
Coenzyme A ◽  
Computational Study

Atypical Protonation States in the Active Site of HIV-1 Protease: A Computational Study

2007 ◽  
Vol 47 (4) ◽  
pp. 1590-1598 ◽  
Author(s):  
Paul Czodrowski ◽  
Christoph A. Sotriffer ◽  
Gerhard Klebe
Keyword(s):  
Active Site ◽  
Computational Study ◽  
Hiv 1

Mechanism-based Inactivation of Coenzyme B12-dependent Diol Dehydratase by 3-Unsaturated 1,2-Diols and Thioglycerol

2008 ◽  
Vol 144 (4) ◽  
pp. 437-446 ◽  
Author(s):  
T. Toraya ◽  
N. Tamura ◽  
T. Watanabe ◽  
M. Yamanishi ◽  
N. Hieda ◽  
...  
Keyword(s):  
Coenzyme B12 ◽  
Diol Dehydratase

Computational study of distortion effect of Fe-porphyrin found as a biological active site

2020 ◽  
Vol 59 (1) ◽  
pp. 010502 ◽  
Author(s):  
Yu Takano ◽  
Hiroko X. Kondo ◽  
Yusuke Kanematsu ◽  
Yasuhiro Imada
Keyword(s):  
Active Site ◽  
Computational Study ◽  
Distortion Effect
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