Topic
Transition state
About: Transition state is a research topic. Over the lifetime, 4978 publications have been published within this topic receiving 117965 citations. The topic is also known as: transition state of elementary reaction.
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TL;DR: The two x-ray structures show explicit enzyme-substrate interactions that discriminate between the ground and the transition states of the reaction and illustrate the partially dissociative geometry of the transition state of phosphoryl transfer and demonstrate the potential applications of metallofluorides for the study of kinase mechanisms.
Abstract: Nucleoside diphosphate kinase reversibly transfers the γ-phosphate of ATP onto its active site histidine. We have investigated the transition state of histidine phosphorylation with the high-resolution crystal structures of the enzyme from Dictyostelium discoideum with MgADP and either aluminium or beryllium fluoride. The bound aluminium fluoride species is the neutral species AlF3 and not the more common AlF4−. AlF3 forms a trigonal bipyramid that makes it an accurate analog of the transition state of the γ-phosphate of ATP undergoing transfer to the catalytic histidine. Its axial ligands are a histidine nitrogen and a β-phosphate oxygen. Beryllium fluoride also binds at the same position and with the same ligands but in a tetrahedral geometry resembling the Michaelis complex rather than the transition state. The two x-ray structures show explicit enzyme–substrate interactions that discriminate between the ground and the transition states of the reaction. They also illustrate the partially dissociative geometry of the transition state of phosphoryl transfer and demonstrate the potential applications of metallofluorides for the study of kinase mechanisms.
112 citations
TL;DR: The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chemical reactions, such as organocatalysis, organometallic catalysis, and photoreactions.
Abstract: In this account, a technical overview of the artificial force induced reaction (AFIR) method is presented. The AFIR method is one of the automated reaction-path search methods developed by the authors, and has been applied extensively to a variety of chemical reactions, such as organocatalysis, organometallic catalysis, and photoreactions. There are two modes in the AFIR method, i.e., a multicomponent mode and a single-component mode. The former has been applied to bimolecular and multicomponent reactions and the latter to unimolecular isomerization and dissociation reactions. Five numerical examples are presented for an Aldol reaction, a Claisen rearrangement, a Co-catalyzed hydroformylation, a fullerene structure search, and a nonradiative decay path search in an electronically excited naphthalene molecule. Finally, possible applications of the AFIR method are discussed.
112 citations
TL;DR: The utilization of enzyme-substrate binding energy in catalysis has been investigated by experiments on mutant tyrosyl-tRNA synthetases that have been generated by site-directed mutagenesis and the apparent binding energies of certain side chains with the tyrosine and nucleotide moieties increase.
Abstract: The utilization of enzyme-substrate binding energy in catalysis has been investigated by experiments on mutant tyrosyl-tRNA synthetases that have been generated by site-directed mutagenesis. The mutants are poorer enzymes because they lack side chains that form hydrogen bonds with ATP and tyrosine during stages of the reaction. The hydrogen bonds are not directly involved in the chemical processes but are at some distance from the seat of reaction. The free energy profiles for the formation of enzyme-bound tyrosyl adenylate and the equilibria between the substrates and products were determined from a combination of pre-steady-state kinetics and equilibrium binding methods. By comparison of the profile of each mutant with wild-type enzyme, a picture is built up of how the course of reaction is affected by the influence of each side chain on the energies of the complexes of the enzyme with substrates, transition states, and intermediates (tyrosyl adenylate). As the activation reaction proceeds, the apparent binding energies of certain side chains with the tyrosine and nucleotide moieties increase, being weakest in the enzyme-substrate complex, stronger in the transition state, and strongest in the enzyme-intermediate complex. Most marked is the interaction of Cys-35 with the 3'-hydroxyl of the ribose. Removal of the side chain of Cys-35 leads to no change in the dissociation constant of ATP but causes a 10-fold lowering of the catalytic rate constant. It contributes no net apparent binding energy in the E X Tyr X ATP complex and stabilizes the transition state by 1.2 kcal/mol and the E X Tyr-AMP complex by 1.6 kcal/mol.(ABSTRACT TRUNCATED AT 250 WORDS)
111 citations
TL;DR: Significantly, experimental and computational studies question the predictability of primary EIEs in these systems based on the notion that deuterium prefers to occupy the highest frequency oscillator, and the applicability of these rules to the interactions of H-H and C-H bonds with a transition metal center is evaluated.
Abstract: Deuterium kinetic isotope effects (KIEs) serve as versatile tools to infer details about reaction mechanisms and the nature of transition states, while equilibrium isotope effects (EIEs) associated with the site preferences of hydrogen and deuterium enable researchers to study aspects of molecular structure. Researchers typically interpret primary deuterium isotope effects based on two simple guidelines: (i) the KIE for an elementary reaction is normal (kH/kD > 1) and (ii) the EIE is dictated by deuterium preferring to be located in the site corresponding to the highest frequency oscillator. In this Account, we evaluate the applicability of these rules to the interactions of H−H and C−H bonds with a transition metal center. Significantly, experimental and computational studies question the predictability of primary EIEs in these systems based on the notion that deuterium prefers to occupy the highest frequency oscillator. In particular, the EIEs for (i) formation of σ-complexes by coordination of H−H and ...
111 citations
TL;DR: The ring polymer molecular dynamics method is used to study the Azzouz-Borgis model for proton transfer between phenol and trimethylamine in liquid methyl chloride and results are discussed in light of the wide body of earlier theoretical work on the model and the considerable range of previously reported values for its proton and deuteron transfer rate coefficients.
Abstract: We have used the ring polymer molecular dynamics method to study the Azzouz–Borgis model for proton transfer between phenol (AH) and trimethylamine (B) in liquid methyl chloride. When the A–H distance is used as the reaction coordinate, the ring polymer trajectories are found to exhibit multiple recrossings of the transition state dividing surface and to give a rate coefficient that is smaller than the quantum transition state theory value by an order of magnitude. This is to be expected on kinematic grounds for a heavy-light-heavy reaction when the light atom transfer coordinate is used as the reaction coordinate, and it clearly precludes the use of transition state theory with this reaction coordinate. As has been shown previously for this problem, a solvent polarization coordinate defined in terms of the expectation value of the proton transfer distance in the ground adiabatic quantum state provides a better reaction coordinate with less recrossing. These results are discussed in light of the wide body of earlier theoretical work on the Azzouz–Borgis model and the considerable range of previously reported values for its proton and deuteron transfer rate coefficients.
109 citations