Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Substrate positioning dynamics (SPD) orients the substrate in the active site, thereby influencing catalytic efficiency. However, it remains unknown whether SPD effects originate primarily from electrostatic perturbation inside the enzyme or can independently mediate catalysis with a significant non-electrostatic component. In this work, we investigated how the non-electrostatic component of SPD affects transition state (TS) stabilization. Using high-throughput enzyme modeling, we selected Kemp eliminase variants with similar electrostatics inside the enzyme but significantly different SPD. The kinetic parameters of these mutants were experimentally characterized. We observed a valley-shaped, two-segment linear correlation between the TS stabilization free energy (converted from kinetic parameters) and substrate positioning index (a metric to quantify SPD). The energy varies by approximately 2 kcal/mol. Favorable SPD was observed for the distal mutant R154W, increasing the proportion of reactive conformations and leading to the lowest activation free energy. These results indicate the substantial contribution of the non-electrostatic component of SPD to enzyme catalytic efficiency.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211065 | PMC |
| http://dx.doi.org/10.1021/acs.jpclett.3c02444 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interpolyelectrolyte complexes of a biguanide cationic polyelectrolyte: formation of core/corona nanoparticles with double-hydrophilic diblock polyanion.
Soft Matter
December 2024
Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 40, Prague 2, Czech Republic.
Biguanide-based cationic polyelectrolytes are used as key components of interpolyelectrolyte complexes bolstering alginate hydrogel microcapsules employed in cell therapies. Nevertheless, electrostatic complexation of these unique polycations has not been studied before. In this study, the interaction between biguanide condensates and anionic polyelectrolytes with carboxylate groups was studied on a model system of a metformin condensate (MFC) and an anionic diblock polyelectrolyte poly(methacrylic acid)--poly(ethylene oxide) (PMAA-PEO).
View Article and Find Full Text PDFSubstrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis.
J Phys Chem Lett
December 2023
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
Substrate positioning dynamics (SPD) orients the substrate in the active site, thereby influencing catalytic efficiency. However, it remains unknown whether SPD effects originate primarily from electrostatic perturbation inside the enzyme or can independently mediate catalysis with a significant non-electrostatic component. In this work, we investigated how the non-electrostatic component of SPD affects transition state (TS) stabilization.
View Article and Find Full Text PDFTheoretical treatment of complex coacervate core micelles: structure and pH-induced disassembly.
Soft Matter
October 2023
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Inorgánica Analítica y Química Física y CONICET-Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Instituto de Química de los Materiales, Ambiente y Energía (INQUIMAE), Pabelló
Complex coacervate core micelles (C3Ms) are supramolecular soft nanostructures formed by the assembly of a block copolymer and an oppositely charged homopolymer. The coacervation of the charged segments in both macromolecules drives the formation of the core of the C3M, while the neutral block of the copolymer forms the corona. This work introduces a molecular theory (MOLT) that predicts the internal structure and stimuli-responsive properties of C3Ms and explicitly considers the chemical architecture of the polyelectrolytes, their acid-based equilibria and electrostatic and non-electrostatic interactions.
View Article and Find Full Text PDFExcitation Energies of Embedded Chromophores from Frozen-Density Embedding Theory Using State-Specific Electron Densities of the Environment.
J Phys Chem A
January 2023
Department of Physical Chemistry, University of Geneva, 30, Quai Ernest-Ansermet, CH-1211 4Genève, Switzerland.
Starting from the Perdew-Levy theorem on extrema of the Hohenberg-Kohn functional, the expression for the vertical excitation energy is derived within the formal framework of Frozen-Density Embedding Theory (FDET) that makes it possible to use state-specific electron densities of the environment (ρ) of an embedded species. The derived general expression involves the embedded wave functions for ground and excited states that are orthogonal and is exact up to quadratic terms in the appropriate density expansion. It can be applied in practice using various methods differing in the treatment of the electron-electron correlation for embedded electrons, the method to evaluate different contributions to the excitation energy, the method to generate state-specific ρ, and the approximation used for the non-electrostatic component of the FDET embedding potential.
View Article and Find Full Text PDFOn the nature of screening in Voorn-Overbeek type theories.
J Chem Phys
June 2022
School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
By using a recently formulated Legendre transform approach to the thermodynamics of charged systems, we explore the general form of the screening length in the Voorn-Overbeek-type theories, which remains valid also in the cases where the entropy of the charged component(s) is not given by the ideal gas form as in the Debye-Hückel theory. The screening length consistent with the non-electrostatic terms in the free energy ansatz for the Flory-Huggins and Voorn-Overbeek type theories, derived from the local curvature properties of the Legendre transform, has distinctly different behavior than the often invoked standard Debye screening length, though it reduces to it in some special cases.
View Article and Find Full Text PDF