Combined Spectroscopic/Computational Study of Binuclear Fe(I)−Fe(I) Complexes:  Implications for the Fully-Reduced Active-Site Cluster of Fe-Only Hydrogenases

2005 ◽  
Vol 44 (6) ◽  
pp. 1794-1809 ◽  
Author(s):  
Adam T. Fiedler ◽  
Thomas C. Brunold
Keyword(s):  
Active Site ◽  
Computational Study ◽  
Site Cluster

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

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

scholarly journals Aldose Reductase Differential Inhibitors in Green Tea

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1003 ◽  
Author(s):  
Francesco Balestri ◽  
Giulio Poli ◽  
Carlotta Pineschi ◽  
Roberta Moschini ◽  
Mario Cappiello ◽  
...  
Keyword(s):  
Gallic Acid ◽  
Green Tea ◽  
Aldose Reductase ◽  
Active Site ◽  
Inhibitory Action ◽  
Computational Study ◽  
Epigallocatechin Gallate ◽  
Polyol Pathway ◽  
Differential Inhibition ◽  
Tea Extract

Aldose reductase (AKR1B1), the first enzyme in the polyol pathway, is likely involved in the onset of diabetic complications. Differential inhibition of AKR1B1 has been proposed to counteract the damaging effects linked to the activity of the enzyme while preserving its detoxifying ability. Here, we show that epigallocatechin gallate (EGCG), one of the most representative catechins present in green tea, acts as a differential inhibitor of human recombinant AKR1B1. A kinetic analysis of EGCG, and of its components, gallic acid (GA) and epigallocatechin (EGC) as inhibitors of the reduction of L-idose, 4-hydroxy2,3-nonenal (HNE), and 3-glutathionyl l-4-dihydroxynonanal (GSHNE) revealed for the compounds a different model of inhibition toward the different substrates. While EGCG preferentially inhibited L-idose and GSHNE reduction with respect to HNE, gallic acid, which was still active in inhibiting the reduction of the sugar, was less active in inhibiting HNE and GSHNE reduction. EGC was found to be less efficient as an inhibitor of AKR1B1 and devoid of any differential inhibitory action. A computational study defined different interactive modes for the three substrates on the AKR1B1 active site and suggested a rationale for the observed differential inhibition. A chromatographic fractionation of an alcoholic green tea extract revealed that, besides EGCG and GA, other components may exhibit the differential inhibition of AKR1B1.

scholarly journals Computational Study of Methane C–H Activation by Main Group and Mixed Main Group–Transition Metal Complexes

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2794
Author(s):  
Carly C. Carter ◽  
Thomas R. Cundari
Keyword(s):  
Transition Metal Complexes ◽  
Active Site ◽  
Density Functional ◽  
Computational Study ◽  
Divalent Metal ◽  
Main Group ◽  
Free Energies ◽  
Functional Theory ◽  
Activation Barriers ◽  
Experimental Values

In the present density functional theory (DFT) research, nine different molecules, each with different combinations of A (triel) and E (divalent metal) elements, were reacted to effect methane C–H activation. The compounds modeled herein incorporated the triels A = B, Al, or Ga and the divalent metals E = Be, Mg, or Zn. The results show that changes in the divalent metal have a much bigger impact on the thermodynamics and methane activation barriers than changes in the triels. The activating molecules that contained beryllium were most likely to have the potential for activating methane, as their free energies of reaction and free energy barriers were close to reasonable experimental values (i.e., ΔG close to thermoneutral, ΔG‡ ~30 kcal/mol). In contrast, the molecules that contained larger elements such as Zn and Ga had much higher ΔG‡. The addition of various substituents to the A–E complexes did not seem to affect thermodynamics but had some effect on the kinetics when substituted closer to the active site.

Base Mechanism to the Hydrolysis of Phosphate Triester Promoted by the Cd2+/Cd2+ Active site of Phosphotriesterase: A Computational Study

2018 ◽  
Vol 57 (10) ◽  
pp. 5888-5902 ◽  
Author(s):  
Marcelo A. Chagas ◽  
Eufrásia S. Pereira ◽  
Marina P. B. Godinho ◽  
Júlio Cosme S. Da Silva ◽  
Willian R. Rocha
Keyword(s):  
Active Site ◽  
Computational Study ◽  
Base Mechanism ◽  
Hydrolysis Of
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