Search results for "Enzyme catalysis"
showing 10 items of 60 documents
Are there dynamical effects in enzyme catalysis? Some thoughts concerning the enzymatic chemical step.
2015
Highlights • The possible role of enzymatic reaction dynamical effects is examined. • Solution reactions usefully inform the issue of dynamical effects in enzymes. • Division into regions containing and away from the transition state is important. • Motions in passage to/from the transition state need not lead to dynamical effects. • Transition State Theory is usually a reasonable description of enzyme kinetics.
Hydrolysis of Phosphotriesters: A Theoretical Analysis of the Enzymatic and Solution Mechanisms
2012
A theoretical study on the alkaline hydrolysis of paraoxon, one of the most popular organophosphorus pesticides, in aqueous solution and in the active site of Pseudomonas diminuta phosphotriesterase (PTE) is presented. Simulations by means of hybrid quantum mechanics/molecular mechanics (QM/MM) potentials show that the hydrolysis of paraoxon takes place through an A(N)D(N) or associative mechanism both in solution and in the active site of PTE. The results correctly reproduce the magnitude of the activation free energies and can be used to rationalize the observed kinetic isotope effects (KIEs) for the hydrolysis of paraoxon in both media. Enzymatic hydrolysis of O,O-diethyl p-chlorophenyl …
Structural Basis and Enzymatic Mechanism of the Biosynthesis of C9- from C10-Monoterpenoid Indole Alkaloids
2009
Cutting carbons: The three-dimensional structure of polyneuridine aldehyde esterase (PNAE) gives insight into the enzymatic mechanism of the biosynthesis of C(9)- from C(10)-monoterpenoid indole alkaloids (see scheme). PNAE is a very substrate-specific serine esterase. It harbors the catalytic triad S87-D216-H244, and is a new member of the alpha/beta-fold hydrolase superfamily. Its novel function leads to the diversification of alkaloid structures.
Quantifying the limits of transition state theory in enzymatic catalysis
2017
Significance Transition state theory (TST) is the most popular theory to calculate the rates of enzymatic reactions. However, in some cases TST could fail due to the violation of the nonrecrossing hypothesis at the transition state. In the present work we show that even for one of the most controversial enzymatic reactions—the hydride transfer catalyzed by dihydrofolate reductase—the error associated to TST represents only a minor correction to the reaction rate. Moreover, this error is actually larger for the reaction in solution than in the enzymatic active site. Based on this finding and on previous studies we propose an “enzymatic shielding” hypothesis which encompasses various aspects …
On Transition Structures for Hydride Transfer Step in Enzyme Catalysis. A Comparative Study on Models of Glutathione Reductase Derived from Semiempir…
1996
As a model of the chemical reactions that take place in the active site of gluthatione reductase, the nature of the molecular mechanism for the hydride transfer step has been characterized by means of accurate quantum chemical characterizations of transition structures. The calculations have been carried out with analytical gradients at AM1 and PM3 semiempirical procedures, ab initio at HF level with 3-21G, 4-31G, 6-31G, and 6-31G basis sets and BP86 and BLYP as density functional methods. The results of this study suggest that the endo relative orientation on the substrate imposed by the active site is optimal in polarizing the C4-Ht bond and situating the system in the neighborhood of the…
Improved Expression of His6-Tagged Strictosidine Synthase cDNA for Chemo-Enzymatic Alkaloid Diversification
2010
Strictosidine synthase (STR1) catalyzes the stereoselective formation of 3alpha(S)-strictosidine from tryptamine and secologanin. Strictosidine is the key intermediate in the biosynthesis of 2,000 plant monoterpenoid indole alkaloids, and it is a key precursor of enzyme-mediated synthesis of alkaloids. An improved expression system is described which leads to optimized His(6)-STR1 synthesis in Escherichia coli. Optimal production of STR1 was achieved by determining the impact of co-expression of chaperones pG-Tf2 and pG-LJE8. The amount and activity of STR1 was doubled in the presence of chaperone pG-Tf2 alone. His(6)-STR1 immobilized on Ni-NTA can be used for enzymatic synthesis of stricto…
Preorganization and reorganization as related factors in enzyme catalysis: the chorismate mutase case.
2003
In this paper a deeper insight into the chorismate-to prephenate-rearrangement, catalyzed by Bacillus subtilis chorismate mutase, is provided by means of a combination of statistical quantum mechanics/molecular mechanics simulation methods and hybrid potential energy surface exploration techniques. The main aim of this work is to present an estimation of the preorganization and reorganization terms of the enzyme catalytic rate enhancement. To analyze the first of these, we have studied different conformational equilibria of chorismate in aqueous solution and in the enzyme active site. Our conclusion is that chorismate mutase preferentially binds the reactive conformer of the substrate--that…
Dicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium as Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols
2009
Dicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium has been prepared and its structure confirmed by X-ray analysis. This complex shows excellent catalytic activity and modest stability against air in racemization reactions of secondary alcohols. In Candida antarctica lipase B (CAL-B) catalyzed dynamic kinetic resolution (DKR) of 1-phenyl- and 1-(furan-2-yl)ethanol compounds, the new complex shows improved performance as an alcohol racemization catalyst in comparison with its well-known pentaphenylcyclopentadienyl analogue, hitherto considered as the leading catalyst candidate. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
On Transition Structures for Hydride Transfer Step: A Theoretical Study of the Reaction Catalyzed by Dihydrofolate Reductase Enzyme
1996
Abstract A theoretical study is presented of the catalytic mechanism of dihydrofolate reductase (DHFR) enzyme based upon the characterization of the transition structure (TS) for the hydride transfer step. Analytical gradients at AM1 and PM3 semiempirical levels have been used to characterize the saddle point of index one (SPi-1) on global energy hypersurface for the hydride transfer in the active site of DHFR enzyme. The geometry, stereochemistry, electronic structure, and transition vector (TV) components associated to SPi-1 are qualitatively computational level independent. The TV amplitudes show primary and secondary isotope effects to be strongly coupled. The geometrical arrangement of…
How a Second Mg2+ Ion Affects the Phosphoryl Transfer Mechanism in a Protein Kinase: A Computational Study
2020
<div>In this contribution, the phosphoryl transfer reaction in CDK2 has been studied in detail considering the presence of an additional Mg2+ ion in the active site. For this purpose, QM/MM (quantum mechanics/molecular mechanics) free energy calculations with the adaptive string method were performed, which showed that indeed the system containing two Mg2+ ions exhibits a lower activation free energy, corroborating the experimental observations.</div>