scholarly journals Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: a QM/MM study

2019 ◽  
Author(s):  
Rodrigo Recabarren ◽  
Edison H. Osorio ◽  
Julio Caballero ◽  
Iñaki Tuñón ◽  
Jans Alzate-Morales
Keyword(s):  
Energy Barrier ◽  
Transfer Reaction ◽  
Theoretical Study ◽  
Phosphoryl Group ◽  
Phosphoryl Transfer ◽  
Cyclin Dependent Kinase ◽  
Peptide Substrate ◽  
Bond Forming ◽  
Potential Energy Barrier ◽  
Charge Analysis

AbstractCyclin-dependent kinase 2 (CDK2) is an important member of the CDK family exerting its most important function in the regulation of the cell cycle. It catalyzes the transfer of the gamma phosphate group from an ATP (adenosine triphosphate) molecule to a Serine/Threonine residue of a peptide substrate. Due to the importance of this enzyme, and protein kinases in general, a detailed understanding of the reaction mechanism is desired. Thus, in this work the phosphoryl transfer reaction catalyzed by CDK2 was revisited and studied by means of hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Our results show that the base-assisted mechanism is preferred over the substrate-assisted pathway, in agreement with a previous theoretical study. The base-assisted mechanism resulted to be dissociative, with a potential energy barrier of 14.3 kcal/mol, very close to the experimental derived value. An interesting feature of the mechanism is the proton transfer from Lys129 to the phosphoryl group at the second transition state, event that could be helping in neutralizing the charge on the phosphoryl group upon the absence of a second Mg2+ ion. Furthermore, important insights into the mechanisms in terms of bond order and charge analysis were provided. These descriptors helped to characterize the synchronicity of bond forming and breaking events, and to characterize charge transfer effects. Local interactions at the active site are key to modulate the charge distribution on the phosphoryl group and therefore alter its reactivity.

The kinetics of proton and deuteron transfer from 1-(4-nitrophenyl)-1-nitroethane to1,8-diazabicyclo[5.4.0]undec-7-ene in aprotic solvents

1982 ◽  
Vol 60 (13) ◽  
pp. 1692-1695 ◽  
Author(s):  
Kenneth T. Leffek ◽  
Przemyslaw Pruszynski
Keyword(s):  
Energy Barrier ◽  
Reaction Rate ◽  
Significant Contribution ◽  
Transfer Reaction ◽  
Isotope Effects ◽  
Activation Parameters ◽  
Proton Transfer Reaction ◽  
Potential Energy Barrier ◽  
Deuteron Transfer ◽  
Kinetics Of

1-(4-Nitrophenyl)-1-nitroethane reacts with the base1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in both acetonitrile and toluene solvents in a normal second-order proton-transfer reaction, in contrast to its behaviour with the base 2,7-dimethoxy-1,8-bis(dimethylamino)naphthalene in acetonitrile.The primary isotope effect, kHlkD = 12.0 at 25° in toluene is very similar to that observed by other workers for the reaction of 4-nitrophenylnitromethane with DBU under the same conditions. In acetonitrile solvent a kHlkD ratio of 7.8 was found at 25 °C. The isotope effects on the activation parameters for the reaction in both solvents indicate that tunnelling of the proton through the potential energy barrier makes a significant contribution to the reaction rate.

scholarly journals Mechanistic insights into the phosphoryl transfer reaction in cyclin-dependent kinase 2: A QM/MM study

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0215793 ◽  
Author(s):  
Rodrigo Recabarren ◽  
Edison H. Osorio ◽  
Julio Caballero ◽  
Iñaki Tuñón ◽  
Jans H. Alzate-Morales
Keyword(s):  
Transfer Reaction ◽  
Phosphoryl Transfer ◽  
Cyclin Dependent Kinase

Structure and activity of phosphoglycerate mutase

1981 ◽  
Vol 293 (1063) ◽  
pp. 121-130 ◽  
Keyword(s):  
Active Site ◽  
Transfer Reaction ◽  
Chemical Kinetic ◽  
Phosphoglycerate Mutase ◽  
Phosphoryl Transfer ◽  
X Ray ◽  
Histidine Residues ◽  
Ping Pong ◽  
Available Information ◽  
Structure And Activity

The structure of yeast phosphoglycerate mutase determined by X-ray crystallographic and amino acid sequence studies has been interpreted in terms of the chemical, kinetic and mechanistic observations made on this enzyme. There are two histidine residues at the active site, with imidazole groups almost parallel to each other and approximately 0.4 nm apart, positioned close to the 2 and 3 positions of the substrate. The simplest interpretation of the available information suggests that a ping-pong type mechanism operates in which at least one of these histidine residues participates in the phosphoryl transfer reaction. The flexible C-terminal region also plays an important role in the enzymic reaction.

Theoretical Study of Iron Heterogeneous Growth on the Surface of C60 Molecule

2014 ◽  
Vol 1081 ◽  
pp. 115-118
Author(s):  
Qi Cheng Liu ◽  
Yun Fang Li
Keyword(s):  
Crystallization Process ◽  
Theoretical Study ◽  
Covalent Bond ◽  
Md Simulations ◽  
Nucleation And Growth ◽  
Bond Forming ◽  
Regular Icosahedron ◽  
Molecule Dynamics ◽  
Molecule Surface ◽  
Regular Closed

Direct molecule dynamics (MD) simulations have also been performed to study heterogeneous nucleation and growth of iron on C60 molecule. The grown mechanism of this crystallization process was explored. The results indicate that 92 iron atoms attach to C60 molecule surface can form new covalent bond, forming a closed regular icosahedron. More atoms grow in layer to form bigger regular closed clathrate base on the structure of former one. As increase of atoms number, there will appear some crystal faces.

An enzymic cleavage and phosphoryl transfer reaction involving monothiolphosphate

1965 ◽  
Vol 109 (2) ◽  
pp. 284-292 ◽  
Author(s):  
E.F. Korman ◽  
J.H. Shaper ◽  
O. Cernichiari ◽  
Roberts A. Smith
Keyword(s):  
Transfer Reaction ◽  
Phosphoryl Transfer

Hybrid-Bistable Vibration Energy Harvester With Adaptive Potential Well

2018 ◽  
Author(s):  
Jinki Kim ◽  
Patrick Dorin ◽  
K. W. Wang
Keyword(s):  
Energy Harvesting ◽  
Potential Energy ◽  
Cantilever Beam ◽  
Potential Barrier ◽  
Energy Barrier ◽  
Electrical Power ◽  
Vibration Energy ◽  
Frequency Spectra ◽  
Potential Energy Barrier ◽  
Piezoelectric Energy

Many common environmental vibration sources exhibit low and broad frequency spectra. In order to exploit such excitations, energy harvesting architectures utilizing nonlinearity, especially bistability, have been widely studied since the energetic interwell oscillations between their stable equilibria can provide enhanced power harvesting capability over a wider bandwidth compared to the linear counterpart. However, one of the limitations of these nonlinear architectures is that the interwell oscillation regime may not be activated for a low excitation level that is not strong enough to overcome the potential energy barrier, thus resulting in low amplitude intrawell response which provides poor energy harvesting performance. While the strategic integration of bistability and additional dynamic elements has shown potential to improve broadband energy harvesting performance by lowering the potential barrier, there is a clear opportunity to further improve the energy harvesting performance by extracting electrical power from the kinetic energy in the additional element that is induced when the potential barrier is lowered. To explore this opportunity and advance the state of the art, this research develops a novel hybrid bistable vibration energy harvesting system with a passive mechanism that not only adaptively lowers the potential energy barrier level to improve broadband performance but also exploits additional means to capture more usable electrical power. The proposed harvester is comprised of a cantilever beam with repulsive magnets, one attached at the free end and the other attached to a linear spring that is axially aligned with the cantilever (a spring-loaded magnet oscillator). This new approach capitalizes on the adaptive bistable potential that is passively realized by the spring-loaded magnet oscillator, which lowers the double-well potential energy barrier thereby facilitating the interwell oscillations of the cantilever across a broad range of excitation conditions, especially for low excitation amplitudes and frequencies. The interwell oscillation of the cantilever beam enhances not only the piezoelectric energy harvesting from the beam but also the electromagnetic energy harvesting from the spring-loaded magnet oscillator by inducing large amplitude vibrations of the magnet oscillator. Numerical investigations found that the proposed architecture yields significantly enhanced energy harvesting performance compared to the conventional bistable harvester with fixed magnet.

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