Search results for "Kinetic isotope effect"

Fourier-transform spectroscopy and deperturbation analysis of the spin-orbit coupled A(1)Σ(+) and b(3)Π states of KRb.

2016

Fourier-transform A(1)Σ(+) - b(3)Π → X(1)Σ(+) laser-induced fluorescence spectra were recorded for the natural mixture of (39,41)K(85,87)Rb isotopologues produced in a heatpipe oven. Overall 4200 rovibronic term values of the spin-orbit coupled A(1)Σ(+) and b(3)Π states were determined with an uncertainty of about 0.01 cm(-1) in the energy range [10 850, 14 200] cm(-1) covering rotational quantum numbers J' ∈ [3, 280]. Direct deperturbation analysis of the A ∼ b complex performed within the framework of the A(1)Σ(+) ∼ b(3)ΠΩ=0,1,2 coupled-channel approach reproduced experimental data with a standard deviation of 0.004 cm(-1). Initial parameters of the internuclear potentials and spin-orbit …

Origin of Enzymatic Kinetic Isotope Effects in Human Purine Nucleoside Phosphorylase

2017

Here we report a study of the effect of heavy isotope labeling on the reaction catalyzed by human purine nucleoside phosphorylase (hPNP) to elucidate the origin of its catalytic effect and of the enzymatic kinetic isotope effect (EKIE). Using quantum mechanical and molecular mechanical (QM/MM) molecular dynamics (MD) simulations, we study the mechanism of the hPNP enzyme and the dynamic effects by means of the calculation of the recrossing transmission coefficient. A free energy surface (FES), as a function of both a chemical and an environmental coordinate, is obtained to show the role of the environment on the chemical reaction. Analysis of reactive and nonreactive trajectories allows us …

Quantum dynamics of 16O in collision with ortho- and para-17O17O

2017

Abstract We report full quantum dynamical observables, such as integral and differential cross sections and rate constants, for the 16 O +  17 O 17 O reactive collision process. We particularly emphasize the effect coming from the nonzero nuclear spin of 17 O, leading to two nuclear spin isomers of 34 O 2 , ortho- and para- 34 O 2 which can be studied independently and behave differently. A comparison with the 16 O +  18 O 18 O collision is given. We find that processes involving 17 O 17 O are always faster than with 18 O 18 O.

Molecular Mechanism of the site-specific self-cleavage of the RNA phosphodiester backbone by a Twister Ribozyme

2017

Published as part of the special collection of articles derived from the 10th Congress on Electronic Structure: Principles and Applications (ESPA-2016). The catalytic activity of some classes of natural RNA, named as ribozymes, has been discovered just in the past decades. In this paper, the cleavage of the RNA phosphodiester backbone has been studied in aqueous solution and in a twister ribozyme from Oryza sativa. The free energy profiles associated with a baseline substrate-assisted mechanism for the reaction in the enzyme and in solution were computed by means of free energy perturbation methods within hybrid QM/MM potentials, describing the chemical system by the M06-2× functional and t…

2018

The origin of substrate preference in promiscuous enzymes was investigated by enzyme isotope labelling of the alcohol dehydrogenase from Geobacillus stearothermophilus (BsADH). At physiological temperature, protein dynamic coupling to the reaction coordinate was insignificant. However, the extent of dynamic coupling was highly substrate-dependent at lower temperatures. For benzyl alcohol, an enzyme isotope effect larger than unity was observed, whereas the enzyme isotope effect was close to unity for isopropanol. Frequency motion analysis on the transition states revealed that residues surrounding the active site undergo substantial displacement during catalysis for sterically bulky alcohol…

Isotopic Effect on the Kinetics of the Belousov-Zhabotinsky Reaction

2007

In this work we present results about the deuterium isotope effect on the global kinetics of a Belousov-Zhabotinsky reaction in batch conditions. A nonlinear dependence of the Induction Period upon the percentage of deuterated reactants was found. The isotopic effect on the bromination reaction of malonic acid was evaluated.

Theoretical Study of Primary Reaction of Pseudozyma antarctica Lipase B as the Starting Point To Understand Its Promiscuity

2014

Pseudozyma antarctica lipase B (PALB) is a serine hydrolase that catalyzes the hydrolysis of carboxylic acid esters in aqueous medium but it has also shown catalytic activity for a plethora of reactions. This promiscuous activity has found widespread applications. In the present paper, the primary reaction of PALB, its native hydrolytic activity, has been studied using hybrid quantum mechanical/molecular mechanical (QM/MM) potentials. Free energy surfaces, obtained from QM/MM Molecular Dynamics (MD) simulations, show that the reaction takes place by means of a multi-step mechanism where the first step, the activation of the carbonyl group of the substrate and the nucleophilic attack of Ser1…

QM/MM Determination of Kinetic Isotope Effects for COMT-Catalyzed Methyl Transfer Does Not Support Compression Hypothesis

2004

Secondary alpha-D3 kinetic isotope effects calculated by the hybrid AM1/TIP3P/CHARMM method for the reaction of S-adenosylmethionine with catecholate anion in aqueous solution and catalyzed by rat liver catechol O-methyltransferase at 298 K are 0.94 and 0.85, respectively, in good accord with experiment. The large inverse effect for the enzymatic reaction is not due to compression but arises from significant increases in the stretching and bending force constants involving the isotopically substituted atoms of the transferring methyl group as between the reactant complex and the transition structure, larger than for the reaction in water.

Insights on the origin of catalysis on glycine N-methyltransferase from computational modeling.

2018

The origin of enzyme catalysis remains a question of debate despite much intense study. We report a QM/MM theoretical study of the SN2 methyl transfer reaction catalyzed by a glycine N-methyltransferase (GNMT) and three mutants to test whether recent experimental observations of rate-constant reductions and variations in inverse secondary α-3H kinetic isotope effects (KIEs) should be attributed to changes in the methyl donor−acceptor distance (DAD): is catalysis due to a compression effect? Semiempirical (AM1) and DFT (M06-2X) methods were used to describe the QM subset of atoms, while OPLS-AA and TIP3P classical force fields were used for the protein and water molecules, respectively. The …

The equilibrium structure of trans-glyoxal from experimental rotational constants and calculated vibration–rotation interaction constants

2003

A total of six high-resolution FT-IR spectra for trans-glyoxal-d2, trans-glyoxal-d1 and trans-glyoxal-13C2 were recorded with a resolution ranging from 0.003 to 0.004 cm−1. By means of a simultaneous ground state combination difference analysis for each of these isotopologues using the Watson Hamiltonian in A-reduction and Ir-representation the ground state rotational constants are obtained. An empirical equilibrium structure is determined for trans-glyoxal using these experimental ground state rotational constants and vibration–rotation interaction constants calculated at the CCSD(T)/cc-pVTZ level of theory. The least-squares fit yields the following structural parameters for trans-glyoxal…