Reaction pathway and rate-determining step in the aminoacylation of tRNAArg catalyzed by the arginyl-tRNA synthetase from yeast

Biochemistry ◽  
1978 ◽  
Vol 17 (18) ◽  
pp. 3740-3746 ◽  
Author(s):  
Alan R. Fersht ◽  
Jean Gangloff ◽  
Guy Dirheimer
Keyword(s):  
Reaction Pathway ◽  
Trna Synthetase ◽  
Rate Determining Step

Reaction Pathway and Rate-Determining Step of the Schmidt Rearrangement/Fragmentation: A Kinetic Study

2012 ◽  
Vol 77 (8) ◽  
pp. 4073-4078 ◽  
Author(s):  
Ryo Akimoto ◽  
Takehiro Tokugawa ◽  
Yutaro Yamamoto ◽  
Hiroshi Yamataka
Keyword(s):  
Kinetic Study ◽  
Reaction Pathway ◽  
Rate Determining Step

scholarly journals Mechanistic Insights into Water-Catalyzed Formation of Levoglucosenone from Anhydrosugar Intermediates by Means of High-Level Theoretical Procedures

2016 ◽  
Vol 69 (9) ◽  
pp. 943 ◽  
Author(s):  
Wenchao Wan ◽  
Li-Juan Yu ◽  
Amir Karton
Keyword(s):  
Activation Energy ◽  
Reaction Mechanism ◽  
Ring Opening ◽  
Reaction Pathway ◽  
Fast Pyrolysis ◽  
Rate Determining Step ◽  
Dehydration Reactions ◽  
High Level ◽  
Multistep Reaction ◽  
Hydration And Dehydration

Levoglucosenone (LGO) is an important anhydrosugar product of fast pyrolysis of cellulose and biomass. We use the high-level G4(MP2) thermochemical protocol to study the reaction mechanism for the formation of LGO from the 1,4:3,6-dianhydro-α-d-glucopyranose (DGP) pyrolysis intermediate. We find that the DGP-to-LGO conversion proceeds via a multistep reaction mechanism, which involves ring-opening, ring-closing, enol-to-keto tautomerization, hydration, and dehydration reactions. The rate-determining step for the uncatalyzed process is the enol-to-keto tautomerization (ΔG‡298 = 68.6 kcal mol–1). We find that a water molecule can catalyze five of the seven steps in the reaction pathway. In the water-catalyzed process, the barrier for the enol-to-keto tautomerization is reduced by as much as 15.1 kcal mol–1, and the hydration step becomes the rate-determining step with an activation energy of ΔG‡298 = 58.1 kcal mol–1.

EXPLORING THE POTENTIAL ENERGY SURFACE OF THE CATALYZED ISOMERIZATION OF NITROSOMETHANE TO FORMALDOXIME

2007 ◽  
Vol 06 (01) ◽  
pp. 187-195 ◽  
Author(s):  
GUO-MING LIANG ◽  
YI REN ◽  
SAN-YAN CHU ◽  
NING-BEW WONG
Keyword(s):  
Activation Energy ◽  
Formic Acid ◽  
Energy Surface ◽  
Reaction Pathway ◽  
Hydroxyl Group ◽  
Rate Determining Step ◽  
Reaction Channels ◽  
Acid Catalyzed ◽  
Favorable Reaction ◽  
The One

The mechanism of the isomerization of nitrosomethane to formaldoxime catalyzed by neutral molecule ( H 2 O and HCOOH ) has been investigated at the level of B3LYP/6-311+G**. Calculated results indicate that the rearrangement from nitrosomethane to more stable trans-formaldoxime can proceed via two different reaction channels, but the favorable reaction pathway catalyzed by water and formic acid is different from the one in the catalyst-free reaction. It is more favorable that the tautomeric reaction involves the formation of cis-formaldoxime and a subsequent rotation about the N – O bond to form trans-formaldoxime in the catalyzed reaction. The activation energy of rate-determining step was reduced from 197.9 kJ/mol to 138.7 kJ/mol in the water-catalyzed reaction and 79.6 kJ/mol in the formic acid-catalyzed reaction, respectively, due to the catalysis of hydroxylic groups, but the catalysis of more acidic hydroxyl group in the latter system has been shown to be more efficient.

scholarly journals Revealing Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes

2020 ◽  
Author(s):  
Aqeel A. Hussein ◽  
Hafiz S. Ali
Keyword(s):  
Phenyl Ring ◽  
Density Functional ◽  
Reaction Pathway ◽  
Phenyl Group ◽  
Functional Theory ◽  
Rate Determining Step ◽  
Rate Limiting Step ◽  
Electron Withdrawing Group ◽  
Catalytic Cycles ◽  
Rate Limiting

<p><a>Density functional theory exploited with the (SMD)-B3LYP-D3/def2-TZVP//B3LYP/6-31G(d),LANL2DZ level of theory is presented to offer mechanistic insights and explications of experimentally intriguing observations in the Au(I)-catalyzed cyclization of cyclic and acyclic acetals of alkynylaldehydes that lead to indenone formation. The reactivity of catalytic cycles with and without methoxy migration is computationally defined when alkyne terminus is phenylated in addition to the unreactive cycle when alkyne terminus is not phenylated. The reaction mechanism of indenone formation proceeds first with coordination of Au(I) to alkyne to initiate the reaction with 1,5-H shift as a rate-determining step and the fastest 1,5-H shift is achieved when one phenyl ring carries electron-donating group and the other one is substituted with electron-withdrawing group. The absence of tethered acetal unit considerably outpaces any 1,5-H shift and instead activates 1,5-methoxy migration, giving methoxy-migrated indenone, with the step of 1,2-OMe shift is a rate-limiting step during reaction pathway. Following 1,5-H shift the cyclization and 1,2-H shift are kinetically and thermodynamically feasible, which are followed by elimination to persist the iterative cycle, but the reactivity of both steps is highly affected by the existence of phenyl group on alkyne terminus. The unreactivity of alkyne terminus being not beared a phenyl ring is due to that the cyclization is thermodynamically disfavorable, subsequently deactivating the 1,2-H shift kinetically and thermodynamically. </a></p>

scholarly journals Mechanism of the Highly Effective Peptide Bond Hydrolysis by MOF808 Catalyst Under Biologically Relevant Conditions

2020 ◽  
Author(s):  
Dragan Conic ◽  
Kristine Pierloot ◽  
Tatjana Parac-Vogt ◽  
Jeremy Harvey
Keyword(s):  
Reaction Pathway ◽  
Metal Organic Framework ◽  
Peptide Bond ◽  
Binding Mode ◽  
Carbonyl Oxygen ◽  
Nucleophilic Attack ◽  
Selective Hydrolysis ◽  
Peptide Bonds ◽  
Biologically Relevant ◽  
Rate Determining Step

Efficient and selective hydrolysis of inert peptide bonds is of paramount importance. MOF-808, a metal-organic framework based on Zr6 nodes, can hydrolyze peptide bonds efficiently under biologically relevant conditions. However, the details of the catalyst structure and of the underlying catalytic reaction mechanism are challenging to establish. By means of DFT calculations we first investigate the speciation of the Zr6 nodes and identify the nature of ligands that bind to the Zr6O8H4-x core in aqueous conditions. The core is predicted to strongly prefer a Zr6O8H4 protonation state and to be predominantly decorated by bridging formate ligands, giving Zr6(μ3-O)4(μ3-OH)4(BTC)2(HCOO)6 and Zr6(μ3-O)4(μ3-OH)4(BTC)2(HCOO)5(OH)(H2O) as the most favorable structures at physiological pH. The GlyGly peptide can bind MOF in several different ways, with the preferred structure involving coordination through the terminal carboxylate analogously to the binding mode of formate ligand. The pre-reactive binding mode in which the amide carbonyl oxygen coordinates the metal core lies 7 kcal higher in free energy. The preferred reaction pathway is predicted to have two close-lying transition states, either of which could be the rate-determining step: nucleophilic attack on the amide carbon atom and C-N bond breaking, with calculated relative free energies of 31 and 32 kcal/mol, respectively. Replacement of formate by water and hydroxide at the Zr6 node is predicted to be possible, but does not appear to play a role in the hydrolysis mechanism.

scholarly journals RNA-assisted catalysis in a protein enzyme: The 2′-hydroxyl of tRNAThr A76 promotes aminoacylation by threonyl-tRNA synthetase

2008 ◽  
Vol 105 (46) ◽  
pp. 17748-17753 ◽  
Author(s):  
Anand Minajigi ◽  
Christopher S. Francklyn
Keyword(s):  
Amino Acid ◽  
Active Site ◽  
Class Ii ◽  
Trna Synthetase ◽  
Hydroxyl Groups ◽  
Acid Activation ◽  
Mutant Proteins ◽  
Amino Acid Activation ◽  
Rate Determining Step ◽  
Aminoacyl Transfer

Aminoacyl-tRNA synthetases (aaRSs) join amino acids to 1 of 2 terminal hydroxyl groups of their cognate tRNAs, thereby contributing to the overall fidelity of protein synthesis. In class II histidyl-tRNA synthetase (HisRS) the nonbridging Sp-oxygen of the adenylate is a potential general base for aminoacyl transfer. To test for conservation of this mechanism in other aaRSs and the role of terminal hydroxyls of tRNA in aminoacyl transfer, we investigated the class II Escherichia coli threonyl-tRNA synthetase (ThrRS). As with other class II aaRSs, the rate-determining step for ThrRS is amino acid activation. In ThrRS, however, the 2′-OH of A76 of tRNAThr and a conserved active-site histidine (His-309) collaborate to catalyze aminoacyl transfer by a mechanism distinct from HisRS. Conserved residues in the ThrRS active site were replaced with alanine, and then the resulting mutant proteins were analyzed by steady-state and rapid kinetics. Nearly all mutants preferentially affected the amino acid activation step, with only a modest effect on aminoacyl transfer. By contrast, H309A ThrRS decreased transfer 242-fold and imposed a kinetic block to CCA accommodation. His-309 hydrogen bonds to the 2′-OH of A76, and substitution of the latter by hydrogen or fluorine decreased aminoacyl transfer by 763- and 94-fold, respectively. The proton relay mechanism suggested by these data to promote aminoacylation is reminiscent of the NAD+-dependent mechanisms of alcohol dehydrogenases and sirtuins and the RNA-mediated catalysis of the ribosomal peptidyl transferase center.

scholarly journals Revealing Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes

2020 ◽  
Author(s):  
Aqeel A. Hussein ◽  
Hafiz S. Ali
Keyword(s):  
Phenyl Ring ◽  
Density Functional ◽  
Reaction Pathway ◽  
Phenyl Group ◽  
Functional Theory ◽  
Rate Determining Step ◽  
Rate Limiting Step ◽  
Electron Withdrawing Group ◽  
Catalytic Cycles ◽  
Rate Limiting

<p><a>Density functional theory exploited with the (SMD)-B3LYP-D3/def2-TZVP//B3LYP/6-31G(d),LANL2DZ level of theory is presented to offer mechanistic insights and explications of experimentally intriguing observations in the Au(I)-catalyzed cyclization of cyclic and acyclic acetals of alkynylaldehydes that lead to indenone formation. The reactivity of catalytic cycles with and without methoxy migration is computationally defined when alkyne terminus is phenylated in addition to the unreactive cycle when alkyne terminus is not phenylated. The reaction mechanism of indenone formation proceeds first with coordination of Au(I) to alkyne to initiate the reaction with 1,5-H shift as a rate-determining step and the fastest 1,5-H shift is achieved when one phenyl ring carries electron-donating group and the other one is substituted with electron-withdrawing group. The absence of tethered acetal unit considerably outpaces any 1,5-H shift and instead activates 1,5-methoxy migration, giving methoxy-migrated indenone, with the step of 1,2-OMe shift is a rate-limiting step during reaction pathway. Following 1,5-H shift the cyclization and 1,2-H shift are kinetically and thermodynamically feasible, which are followed by elimination to persist the iterative cycle, but the reactivity of both steps is highly affected by the existence of phenyl group on alkyne terminus. The unreactivity of alkyne terminus being not beared a phenyl ring is due to that the cyclization is thermodynamically disfavorable, subsequently deactivating the 1,2-H shift kinetically and thermodynamically. </a></p>

scholarly journals Mechanism of the Highly Effective Peptide Bond Hydrolysis by MOF808 Catalyst Under Biologically Relevant Conditions

2020 ◽  
Author(s):  
Dragan Conic ◽  
Kristine Pierloot ◽  
Tatjana Parac-Vogt ◽  
Jeremy Harvey
Keyword(s):  
Reaction Pathway ◽  
Metal Organic Framework ◽  
Peptide Bond ◽  
Binding Mode ◽  
Carbonyl Oxygen ◽  
Nucleophilic Attack ◽  
Selective Hydrolysis ◽  
Peptide Bonds ◽  
Biologically Relevant ◽  
Rate Determining Step

Efficient and selective hydrolysis of inert peptide bonds is of paramount importance. MOF-808, a metal-organic framework based on Zr6 nodes, can hydrolyze peptide bonds efficiently under biologically relevant conditions. However, the details of the catalyst structure and of the underlying catalytic reaction mechanism are challenging to establish. By means of DFT calculations we first investigate the speciation of the Zr6 nodes and identify the nature of ligands that bind to the Zr6O8H4-x core in aqueous conditions. The core is predicted to strongly prefer a Zr6O8H4 protonation state and to be predominantly decorated by bridging formate ligands, giving Zr6(μ3-O)4(μ3-OH)4(BTC)2(HCOO)6 and Zr6(μ3-O)4(μ3-OH)4(BTC)2(HCOO)5(OH)(H2O) as the most favorable structures at physiological pH. The GlyGly peptide can bind MOF in several different ways, with the preferred structure involving coordination through the terminal carboxylate analogously to the binding mode of formate ligand. The pre-reactive binding mode in which the amide carbonyl oxygen coordinates the metal core lies 7 kcal higher in free energy. The preferred reaction pathway is predicted to have two close-lying transition states, either of which could be the rate-determining step: nucleophilic attack on the amide carbon atom and C-N bond breaking, with calculated relative free energies of 31 and 32 kcal/mol, respectively. Replacement of formate by water and hydroxide at the Zr6 node is predicted to be possible, but does not appear to play a role in the hydrolysis mechanism.

Sign in / Sign up

Export Citation Format

Share Document