scholarly journals Theoretical Studies of the Self Cleavage Pistol Ribozyme Mechanism

2021 ◽  
Author(s):  
Natalia Serrano-Aparicio ◽  
Katarzyna Świderek ◽  
Iñaki Tuñón ◽  
Vicent Moliner ◽  
Joan Bertran
Keyword(s):  
Active Site ◽  
Catalytic Mechanism ◽  
Computational Study ◽  
Md Simulations ◽  
Canonical System ◽  
The Self ◽  
Artificial Enzymes ◽  
Theoretical Studies ◽  
Mechanism Analysis ◽  
Experimental And Theoretical Studies

AbstractRibozymes are huge complex biological catalysts composed of a combination of RNA and proteins. Nevertheless, there is a reduced number of small ribozymes, the self-cleavage ribozymes, that are formed just by RNA and, apparently, they existed in cells of primitive biological systems. Unveiling the details of these “fossils” enzymes can contribute not only to the understanding of the origins of life but also to the development of new simplified artificial enzymes. A computational study of the reactivity of the pistol ribozyme carried out by means of classical MD simulations and QM/MM hybrid calculations is herein presented to clarify its catalytic mechanism. Analysis of the geometries along independent MD simulations with different protonation states of the active site basic species reveals that only the canonical system, with no additional protonation changes, renders reactive conformations. A change in the coordination sphere of the Mg2+ ion has been observed during the simulations, which allows proposing a mechanism to explain the unique mode of action of the pistol ribozyme by comparison with other ribozymes. The present results are at the center of the debate originated from recent experimental and theoretical studies on pistol ribozyme.

Theoretical investigation of aerobic and anaerobic oxidative inactivation of the [NiFe]-hydrogenase active site

2018 ◽  
Vol 20 (3) ◽  
pp. 1693-1706 ◽  
Author(s):  
Raffaella Breglia ◽  
Claudio Greco ◽  
Piercarlo Fantucci ◽  
Luca De Gioia ◽  
Maurizio Bruschi
Keyword(s):  
Theoretical Investigation ◽  
Active Site ◽  
Theoretical Studies ◽  
Oxidative Inactivation ◽  
Production Processes ◽  
Experimental And Theoretical Studies ◽  
Aerobic And Anaerobic

The extraordinary capability of [NiFe]-hydrogenases to catalyse the reversible interconversion of protons and electrons into dihydrogen (H2) has stimulated numerous experimental and theoretical studies addressing the direct utilization of these enzymes in H2 production processes.

scholarly journals Revealing the Intrinsic Peroxidase-Like Catalytic Mechanism of Heterogeneous Single-Atom Co–MoS2

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Wang ◽  
Kun Qi ◽  
Shansheng Yu ◽  
Guangri Jia ◽  
Zhiliang Cheng ◽  
...  
Keyword(s):  
High Performance ◽  
Catalytic Mechanism ◽  
Single Atom ◽  
Theoretical Studies ◽  
The Novel ◽  
Peroxidase Mimic ◽  
Adsorption Energies ◽  
Experimental And Theoretical Studies ◽  
Transfer Mechanisms ◽  
Different Parts

AbstractThe single-atom nanozyme is a new concept and has tremendous prospects to become a next-generation nanozyme. However, few studies have been carried out to elucidate the intrinsic mechanisms for both the single atoms and the supports in single-atom nanozymes. Herein, the heterogeneous single-atom Co–MoS2 (SA Co–MoS2) is demonstrated to have excellent potential as a high-performance peroxidase mimic. Because of the well-defined structure of SA Co–MoS2, its peroxidase-like mechanism is extensively interpreted through experimental and theoretical studies. Due to the different adsorption energies of substrates on different parts of SA Co–MoS2 in the peroxidase-like reaction, SA Co favors electron transfer mechanisms, while MoS2 relies on Fenton-like reactions. The different catalytic pathways provide an intrinsic understanding of the remarkable performance of SA Co–MoS2. The present study not only develops a new kind of single-atom catalyst (SAC) as an elegant platform for understanding the enzyme-like activities of heterogeneous nanomaterials but also facilitates the novel application of SACs in biocatalysis.

Experimental and theoretical studies on the self-motion of a phenanthroline disk coupled with complex formation

2010 ◽  
Vol 12 (7) ◽  
pp. 1557 ◽  
Author(s):  
Keita Iida ◽  
Nobuhiko J. Suematsu ◽  
Yumi Miyahara ◽  
Hiroyuki Kitahata ◽  
Masaharu Nagayama ◽  
...  
Keyword(s):  
Complex Formation ◽  
The Self ◽  
Theoretical Studies ◽  
Self Motion ◽  
Experimental And Theoretical Studies

scholarly journals Galactokinase promiscuity: a question of flexibility?

2016 ◽  
Vol 44 (1) ◽  
pp. 116-122 ◽  
Author(s):  
Megan McAuley ◽  
Helena Kristiansson ◽  
Meilan Huang ◽  
Angel L. Pey ◽  
David J. Timson
Keyword(s):  
Active Site ◽  
Catalytic Mechanism ◽  
High Specificity ◽  
Enzyme Engineering ◽  
Structural Modifications ◽  
Leloir Pathway ◽  
Wide Range ◽  
Base Mechanism ◽  
Viable Approach ◽  
Experimental And Theoretical Studies

Galactokinase catalyses the first committed step of the Leloir pathway, i.e. the ATP-dependent phosphorylation of α-D-galactose at C1-OH. Reduced galactokinase activity results in the inherited metabolic disease type II galactosaemia. However, inhibition of galactokinase is considered a viable approach to treating more severe forms of galactosaemia (types I and III). Considerable progress has been made in the identification of high affinity, selective inhibitors. Although the structure of galactokinase from a variety of species is known, its catalytic mechanism remains uncertain. Although the bulk of evidence suggests that the reaction proceeds via an active site base mechanism, some experimental and theoretical studies contradict this. The enzyme has potential as a biocatalyst in the production of sugar 1-phosphates. This potential is limited by its high specificity. A variety of approaches have been taken to identify galactokinase variants which are more promiscuous. These have broadened galactokinase's specificity to include a wide range of D- and L-sugars. Initial studies suggest that some of these alterations result in increased flexibility at the active site. It is suggested that modulation of protein flexibility is at least as important as structural modifications in determining the success or failure of enzyme engineering.

Structures of c-di-GMP/cGAMP degrading phosphodiesterase VcEAL: identification of a novel conformational switch and its implication

2019 ◽  
Vol 476 (21) ◽  
pp. 3333-3353 ◽  
Author(s):  
Malti Yadav ◽  
Kamalendu Pal ◽  
Udayaditya Sen
Keyword(s):  
Active Site ◽  
Metal Binding ◽  
Metal Ion ◽  
Triosephosphate Isomerase ◽  
Catalytic Mechanism ◽  
Degradation Mechanism ◽  
Structural Basis ◽  
Conserved Residues ◽  
Phosphodiester Bond ◽  
Cyclic Dinucleotides

Cyclic dinucleotides (CDNs) have emerged as the central molecules that aid bacteria to adapt and thrive in changing environmental conditions. Therefore, tight regulation of intracellular CDN concentration by counteracting the action of dinucleotide cyclases and phosphodiesterases (PDEs) is critical. Here, we demonstrate that a putative stand-alone EAL domain PDE from Vibrio cholerae (VcEAL) is capable to degrade both the second messenger c-di-GMP and hybrid 3′3′-cyclic GMP–AMP (cGAMP). To unveil their degradation mechanism, we have determined high-resolution crystal structures of VcEAL with Ca2+, c-di-GMP-Ca2+, 5′-pGpG-Ca2+ and cGAMP-Ca2+, the latter provides the first structural basis of cGAMP hydrolysis. Structural studies reveal a typical triosephosphate isomerase barrel-fold with substrate c-di-GMP/cGAMP bound in an extended conformation. Highly conserved residues specifically bind the guanine base of c-di-GMP/cGAMP in the G2 site while the semi-conserved nature of residues at the G1 site could act as a specificity determinant. Two metal ions, co-ordinated with six stubbornly conserved residues and two non-bridging scissile phosphate oxygens of c-di-GMP/cGAMP, activate a water molecule for an in-line attack on the phosphodiester bond, supporting two-metal ion-based catalytic mechanism. PDE activity and biofilm assays of several prudently designed mutants collectively demonstrate that VcEAL active site is charge and size optimized. Intriguingly, in VcEAL-5′-pGpG-Ca2+ structure, β5–α5 loop adopts a novel conformation that along with conserved E131 creates a new metal-binding site. This novel conformation along with several subtle changes in the active site designate VcEAL-5′-pGpG-Ca2+ structure quite different from other 5′-pGpG bound structures reported earlier.

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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