scholarly journals Computational Study of the pKa Values of Potential Catalytic Residues in the Active Site of Monoamine Oxidase B

2012 ◽  
Vol 8 (10) ◽  
pp. 3864-3870 ◽  
Author(s):  
Rok Borštnar ◽  
Matej Repič ◽  
Shina Caroline Lynn Kamerlin ◽  
Robert Vianello ◽  
Janez Mavri
Keyword(s):  
Monoamine Oxidase ◽  
Active Site ◽  
Computational Study ◽  
Monoamine Oxidase B ◽  
Pka Values ◽  
Catalytic Residues

scholarly journals Why does the Y326I mutant of monoamine oxidase B decompose an endogenous amphetamine at a slower rate than the wild type enzyme? Reaction step elucidated by multiscale molecular simulations

2018 ◽  
Vol 20 (6) ◽  
pp. 4181-4188 ◽  
Author(s):  
Domen Pregeljc ◽  
Urška Jug ◽  
Janez Mavri ◽  
Jernej Stare
Keyword(s):  
Monoamine Oxidase ◽  
Active Site ◽  
Molecular Simulations ◽  
Enzyme Reaction ◽  
Monoamine Oxidase B ◽  
Wild Type ◽  
Reaction Step ◽  
Wild Type Enzyme ◽  
Mao B

Mutated MAO B enzyme decomposes phenylethylamine at slower rate due to changed interactions in the active site.

Irreversible Inhibition of Monoamine Oxidase B by the Antiparkinsonian Medicines Rasagiline and Selegiline: A Computational Study

2011 ◽  
Vol 2011 (32) ◽  
pp. 6419-6433 ◽  
Author(s):  
Rok Borštnar ◽  
Matej Repič ◽  
Mojca Kržan ◽  
Janez Mavri ◽  
Robert Vianello
Keyword(s):  
Monoamine Oxidase ◽  
Computational Study ◽  
Monoamine Oxidase B ◽  
Irreversible 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.

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