scholarly journals Evidence for an N-halohistidyl Intermediate in the Catalytic Cycle of Vanadium Chloroperoxidase (VCPO) and an Artificial Enzyme derived from VCPO: A Computational Investigation

2021 ◽  
Author(s):  
Gregory Anderson ◽  
Raghu Nath Behera ◽  
Ravi Gomatam
Keyword(s):  
Catalytic Mechanism ◽  
Catalytic Cycle ◽  
Artificial Enzymes ◽  
Free Energy Barrier ◽  
Artificial Enzyme ◽  
Natural Production ◽  
Natural Enzyme ◽  
Catalytic Role ◽  
Acidic Conditions ◽  
Key Steps

Vanadium haloperoxidases play an important catalytic role in the natural production of antibiotics which are difficult to make in the laboratory. Understanding the catalytic mechanism of these enzymes will aide in the production of artificial enzymes useful in bioengineering the synthesis of drugs and useful chemicals. However, the catalytic mechanism remains not fully understood yet. In this paper, we investigate one of the key steps of the catalytic mechanism using QM/MM. Our investigation reveals a new N-haloxy histidyl intermediate in the catalytic cycle of vanadium chloroperoxidase (VCPO). This new intermediate, in turn, yields an explanation for the known inhibition of the enzyme by substrate under acidic conditions (pH<4). Additionally, we examine the possibility of replacing V in VCPO by Nb or Ta using QM modeling. We report the new result that the Gibbs free energy barrier of several steps of the catalytic cycle are lower in the case of artificial enzymes, incorporating NbO43- or TaO43- instead of VO43-. Our results suggest that these new artificial enzymes may catalyze the oxidation of halide faster than the natural enzyme.

Fe-N-C Artificial Enzyme: Activation of Oxygen for Dehydrogenation and Monoxygenation of Organic Substrates under Mild Condition and Cancer Therapeutic Application

2018 ◽  
Author(s):  
Fei He ◽  
Li Mi ◽  
Yanfei Shen ◽  
Toshiyuki Mori ◽  
Songqin Liu ◽  
...  
Keyword(s):  
Mild Condition ◽  
Enzyme Activation ◽  
Artificial Enzymes ◽  
Organic Substrates ◽  
Artificial Enzyme ◽  
Therapeutic Application ◽  
Highly Efficient ◽  
Activation Of Oxygen

Developing highly efficient artificial enzymes that directly employ O<sub>2</sub> as terminal oxidant has long been pursued but has rarely achieved yet. We report Fe-N-C has unusual enzyme-like activity in both dehydrogenation and monoxygenation of organic substrates with ~100% selectivity by direct using O<sub>2</sub>.

DFT study on the hydrolysis of metsulfuron-methyl: A sulfonylurea herbicide

2018 ◽  
Vol 17 (08) ◽  
pp. 1850050 ◽  
Author(s):  
Qiuhan Luo ◽  
Gang Li ◽  
Junping Xiao ◽  
Chunhui Yin ◽  
Yahui He ◽  
...  
Keyword(s):  
Free Energy ◽  
Water Molecule ◽  
Carbonyl Group ◽  
Energy Barrier ◽  
Density Functional ◽  
Free Energy Barrier ◽  
Functional Theory ◽  
Metsulfuron Methyl ◽  
Catalytic Role ◽  
Hydrolysis Of

Sulfonylureas are an important group of herbicides widely used for a range of weeds and grasses control particularly in cereals. However, some of them tend to persist for years in environments. Hydrolysis is the primary pathway for their degradation. To understand the hydrolysis behavior of sulfonylurea herbicides, the hydrolysis mechanism of metsulfuron-methyl, a typical sulfonylurea, was investigated using density functional theory (DFT) at the B3LYP/6-31[Formula: see text]G(d,p) level. The hydrolysis of metsulfuron-methyl resembles nucleophilic substitution by a water molecule attacking the carbonyl group from aryl side (pathway a) or from heterocycle side (pathway b). In the direct hydrolysis, the carbonyl group is directly attacked by one water molecule to form benzene sulfonamide or heterocyclic amine; the free energy barrier is about 52–58[Formula: see text]kcal[Formula: see text]mol[Formula: see text]. In the autocatalytic hydrolysis, with the second water molecule acting as a catalyst, the free energy barrier, which is about 43–45[Formula: see text]kcal[Formula: see text]mol[Formula: see text], is remarkably reduced by about 11[Formula: see text]kcal[Formula: see text]mol[Formula: see text]. It is obvious that water molecules play a significant catalytic role during the hydrolysis of sulfonylureas.

scholarly journals Synergistic Catalysis of Tandem Michael Addition/Enantioselective Protonation Reactions by an Artificial Enzyme

2021 ◽  
Author(s):  
Zhi Zhou ◽  
Gerard Roelfes
Keyword(s):  
Lewis Acid ◽  
Michael Addition ◽  
Conjugate Addition ◽  
Chiral Center ◽  
Artificial Enzymes ◽  
Artificial Enzyme ◽  
Synergistic Catalysis ◽  
Protonation Reaction ◽  
Stereochemical Control ◽  
Catalytic Sites

Enantioselective protonation is conceptually one of the most attractive methods to generate an α-chiral center. However, enantioselective protonation presents major challenges, especially in water as a solvent. Herein, we report an artificial enzyme catalyzed tandem Michael addition and enantioselective protonation reaction of α-substituted acroleins with 2-acyl imidazole derivatives in water. The artificial enzyme uses a synergistic combination of two abiological catalytic sites: a genetically encoded non-canonical p-aminophenylalanine residue and a Lewis acid Cu(II) complex. The exquisite stereochemical control achieved in the protonation of the transient enamine intermediate generated by conjugate addition of the Michael donor is illustrated by the >20:1 dr and up to >99% ee obtained for the products. These results illustrate the potential of exploiting synergistic catalysis in artificial enzymes for challenging reactions.<br>

scholarly journals Unlocking Iminium Catalysis in Artificial Enzymes to Create a Friedel-Crafts Alkylase

2021 ◽  
Author(s):  
Reuben B. Leveson-Gower ◽  
Zhi Zhou ◽  
Ivana Drienovská ◽  
Gerard Roelfes
Keyword(s):  
Artificial Enzymes ◽  
Artificial Enzyme ◽  
Triple Mutant ◽  
Protein Scaffold ◽  
Rate Acceleration ◽  
Iminium Ion ◽  
Canonical Amino Acid ◽  
Catalytic Reactivity ◽  
Ion Species ◽  
Kinetics Of

We show that the incorporation of the non-canonical amino acid para-aminophenylalanine (pAF) into the non-enzymatic protein scaffold LmrR creates a proficient and stereoselective artificial enzyme (LmrR_pAF) for the vinylogous Friedel-crafts alkylation between alpha, beta-unsaturated aldehydes and indoles. pAF acts as a catalytic residue, activating enal substrates towards conjugate addition via the formation of intermediate iminium ion species, whilst the protein scaffold provides rate acceleration and enantio-induction. Improved LmrR_pAF varants were identified by direted evolution advised by alanine-scanning to obtain a triple mutant that provided higher yields and enantioselectivities for a range of enals and indoles. Analys of Michaelis-Menten kinetics of LmrR-pAF and tevolved mutants reveals that new activities emerge via evolutionary pathways that diverge from one another and specialise catalytic reactivity.<br>

Co3O4@CeO2 hybrid flower-like microspheres: a strong synergistic peroxidase-mimicking artificial enzyme with high sensitivity for glucose detection

2017 ◽  
Vol 5 (4) ◽  
pp. 720-730 ◽  
Author(s):  
Deshetti Jampaiah ◽  
T. Srinivasa Reddy ◽  
Victoria E. Coyle ◽  
Ayman Nafady ◽  
Suresh K. Bhargava
Keyword(s):  
High Sensitivity ◽  
Artificial Enzymes ◽  
Glucose Detection ◽  
Selective Detection ◽  
Artificial Enzyme

Herein, we demonstrate strong synergistic Co3O4@CeO2 hybrid microspheres as peroxidase mimicking artificial enzymes for the sensitive and selective detection of glucose.

New class of artificial enzyme composed of Mn-porphyrin, imidazole, and cucurbit[10]uril toward use as a therapeutic antioxidant

2018 ◽  
Vol 6 (43) ◽  
pp. 7050-7059 ◽  
Author(s):  
Riku Kubota ◽  
Taiga Takabe ◽  
Kohe Arima ◽  
Hideaki Taniguchi ◽  
Shoichiro Asayama ◽  
...  
Keyword(s):  
Artificial Enzymes ◽  
Artificial Enzyme ◽  
New Class

In this study, we investigated a new class of artificial enzymes composed of Mn-porphyrin, imidazole, and cucurbit[10]uril (CB[10]) toward therapeutic antioxidants.

scholarly journals Bioinspired Design and Computational Prediction of SCS Nickel Pincer Complexes for Hydrogenation of Carbon Dioxide

Catalysts ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 319
Author(s):  
Xiaoyun Liu ◽  
Bing Qiu ◽  
Xinzheng Yang
Keyword(s):  
Free Energy ◽  
Formic Acid ◽  
Functional Groups ◽  
Density Functional ◽  
Catalytic Mechanism ◽  
Activation Mechanism ◽  
Free Energy Barrier ◽  
Energy Barriers ◽  
Hydrogenation Of Co2 ◽  
Model Complex

Inspired by the structures of the active site of lactate racemase and H2 activation mechanism of mono-iron hydrogenase, we proposed a series of sulphur–carbon–sulphur (SCS) nickel complexes and computationally predicted their potentials for catalytic hydrogenation of CO2. Density functional theory calculations reveal a metal–ligand cooperated mechanism with the participation of a sulfur atom in the SCS pincer ligand as a proton receiver for the heterolytic cleavage of H2. For all newly proposed complexes containing functional groups with different electron-donating and withdrawing abilities in the SCS ligand, the predicted free energy barriers for the hydrogenation of CO2 to formic acid are in a range of 22.2–25.5 kcal/mol in water. Such a small difference in energy barriers indicates limited contributions of those functional groups to the charge density of the metal center. We further explored the catalytic mechanism of the simplest model complex for hydrogenation of formic acid to formaldehyde and obtained a total free energy barrier of 34.6 kcal/mol for the hydrogenation of CO2 to methanol.

scholarly journals Synergistic Catalysis of Tandem Michael Addition/Enantioselective Protonation Reactions by an Artificial Enzyme

2021 ◽  
Author(s):  
Zhi Zhou ◽  
Gerard Roelfes
Keyword(s):  
Lewis Acid ◽  
Michael Addition ◽  
Conjugate Addition ◽  
Chiral Center ◽  
Artificial Enzymes ◽  
Artificial Enzyme ◽  
Synergistic Catalysis ◽  
Protonation Reaction ◽  
Stereochemical Control ◽  
Catalytic Sites

Enantioselective protonation is conceptually one of the most attractive methods to generate an α-chiral center. However, enantioselective protonation presents major challenges, especially in water as a solvent. Herein, we report an artificial enzyme catalyzed tandem Michael addition and enantioselective protonation reaction of α-substituted acroleins with 2-acyl imidazole derivatives in water. The artificial enzyme uses a synergistic combination of two abiological catalytic sites: a genetically encoded non-canonical p-aminophenylalanine residue and a Lewis acid Cu(II) complex. The exquisite stereochemical control achieved in the protonation of the transient enamine intermediate generated by conjugate addition of the Michael donor is illustrated by the >20:1 dr and up to >99% ee obtained for the products. These results illustrate the potential of exploiting synergistic catalysis in artificial enzymes for challenging reactions.<br>

scholarly journals Structure of Allium lachrymatory factor synthase elucidates catalysis on sulfenic acid substrate

2017 ◽  
Author(s):  
Takatoshi Arakawa ◽  
Yuta Sato ◽  
Jumpei Takabe ◽  
Noriya Masamura ◽  
Masahiro Kato ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Active Site ◽  
Active Sites ◽  
Catalytic Mechanism ◽  
Sigmatropic Rearrangement ◽  
Natural Production ◽  
Lachrymatory Factor ◽  
Biological Decomposition ◽  
Key Residues ◽  
Lachrymatory Factor Synthase

AbstractNatural lachrymatory effects are invoked by small volatile S-oxide compounds. They are produced through alkene sulfenic acids by the action of lachrymatory factor synthase (LFS). Here we present the crystal structures of onion LFS (AcLFS) revealed in solute-free and two solute-stabilized forms. Each structure adopts a single seven-stranded helix-grip fold possessing an internal pocket. Mutagenesis analysis localized the active site to a layer near the bottom of the pocket, which is adjacent to the deduced key residues Arg71, Glu88, and Tyr114. Solute molecules visible on the active site have suggested that AcLFS accepts various small alcohol compounds as well as its natural substrate, and they inhibit this substrate according to their chemistry. Structural homologs have been found in the SRPBCC superfamily, and comparison of the active sites has demonstrated that the electrostatic potential unique to AcLFS could work in capturing the substrate in its specific state. Finally, we propose a rational catalytic mechanism based on intramolecular proton shuttling in which the microenvironment of AcLFS can bypass the canonical [1,4]-sigmatropic rearrangement principle established by microwave studies. Beyond revealing how AcLFS generates the lachrymatory compound, this study provides insights into the molecular machinery dealing with highly labile organosulfur species.Significance statementCrushing of onion liberates a volatile compound, syn-propanethial S-oxide (PTSO), which causes lachrymatory effect on humans. We present the crystal structures of onion LFS (AcLFS), the enzyme responsible for natural production of PTSO. AcLFS features a barrel-like fold, and mutagenic and inhibitory analyses revealed that the key residues are present in the central pocket, harboring highly concentrated aromatic residues plus a dyad motif. The architecture of AcLFS is widespread among proteins with various biological functions, such as abscisic acid receptors and polyketide cyclases, and comparisons with these homologs indicate that unique steric and electronic properties maintain the pocket as a reaction compartment. We propose the molecular mechanism behind PTSO generation and shed light on biological decomposition of short-lived sulfur species.

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