EMPIRICAL VALENCE BOND CALCULATIONS OF ENZYME CATALYSIS

1981 ◽  
Vol 367 (1 Quantum Chemi) ◽  
pp. 370-382 ◽  
Author(s):  
A. Warshel ◽  
R. M. Weiss
Keyword(s):  
Enzyme Catalysis ◽  
Valence Bond ◽  
Empirical Valence Bond

scholarly journals ThermoSlope: A Software for Determining Thermodynamic Parameters from Single Steady-State Experiments

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7155
Author(s):  
Bjarte Aarmo Lund ◽  
Bjørn Olav Brandsdal
Keyword(s):  
Temperature Dependence ◽  
Thermodynamic Parameters ◽  
Enzyme Catalysis ◽  
Traditional Approach ◽  
Extreme Environments ◽  
Valence Bond ◽  
Activation Parameters ◽  
Gradual Change ◽  
Empirical Valence Bond ◽  
Wide Range

The determination of the temperature dependence of enzyme catalysis has traditionally been a labourious undertaking. We have developed a new approach to the classical Arrhenius parameter estimation by fitting the change in velocity under a gradual change in temperature. The evaluation with a simulated dataset shows that the approach is valid. The approach is demonstrated as a useful tool by characterizing the Bacillus pumilus LipA enzyme. Our results for the lipase show that the enzyme is psychrotolerant, with an activation energy of 15.3 kcal/mol for the chromogenic substrate para-nitrophenyl butyrate. Our results demonstrate that this can produce equivalent curves to the traditional approach while requiring significantly less sample, labour and time. Our method is further validated by characterizing three α-amylases from different species and habitats. The experiments with the α-amylases show that the approach works over a wide range of temperatures and clearly differentiates between psychrophilic, mesophilic and thermophilic enzymes. The methodology is released as an open-source implementation in Python, available online or used locally. This method of determining the activation parameters can make studies of the temperature dependence of enzyme catalysis more widely adapted to understand how enzymes have evolved to function in extreme environments. Moreover, the thermodynamic parameters that are estimated serve as functional validations of the empirical valence bond calculations of enzyme catalysis.

scholarly journals Histidine protonation states are key in the LigI catalytic reaction mechanism

2021 ◽  
Author(s):  
LINA ZHAO ◽  
Dibyendu Mondal ◽  
Weifeng Li ◽  
Yuguang Mu ◽  
Philipp Kaldis
Keyword(s):  
Active Site ◽  
Enzyme Catalysis ◽  
Valence Bond ◽  
Free Energy Calculations ◽  
Active Site Residues ◽  
Protonation State ◽  
Empirical Valence Bond ◽  
Hydrolysis Of ◽  
Catalytic Reaction Mechanism

Lignin is one of the world’s most abundant organic polymers, and 2-pyrone-4,6-dicarboxylate lactonase (LigI) catalyzes the hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) in the degradation of lignin. The pH has profound effects on enzyme catalysis and therefore we studied this in the context of LigI. We found that changes of the pH mostly affects surface residues, while the residues at the active site are more subject to changes of the surrounding microenvironment. In accordance with this, a high pH facilitates the deprotonation of the substrate. Detailed free energy calculations by the empirical valence bond (EVB) approach revealed that the overall hydrolysis reaction is more likely when the three active site histidines (His31, His33 and His180) are protonated at the ɛ site, however, protonation at the δ site may be favored during specific steps of reaction. Our studies have uncovered the determinant role of the protonation state of the active site residues His31, His33 and His180 in the hydrolysis of PDC.

scholarly journals Uncovering the Role of Key Active Site Side Chains in Catalysis: An Extended Brønsted Relationship for Substrate Deprotonation Catalysed by Wild-Type and Variants of Triosephosphate Isomerase

2019 ◽  
Author(s):  
Yashraj S. Kulkarni ◽  
Tina L. Amyes ◽  
John Richard ◽  
Shina Caroline Lynn Kamerlin
Keyword(s):  
Active Site ◽  
Triosephosphate Isomerase ◽  
Valence Bond ◽  
Side Chains ◽  
Wild Type ◽  
Empirical Valence Bond

Manuscript and supporting information outlining an analysis of an extended Brønsted relationship obtained from empirical valence bond simulations of substrate deprotonation catalyzed by wild-type and mutant variants of triosephosphate isomerase.

scholarly journals Empirical Valence Bond Simulations Suggest a Direct Hydride Transfer Mechanism for Human Diamine Oxidase

ACS Omega ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 3665-3674 ◽  
Author(s):  
Aleksandra Maršavelski ◽  
Dušan Petrović ◽  
Paul Bauer ◽  
Robert Vianello ◽  
Shina Caroline Lynn Kamerlin
Keyword(s):  
Diamine Oxidase ◽  
Valence Bond ◽  
Hydride Transfer ◽  
Transfer Mechanism ◽  
Empirical Valence Bond ◽  
Human Diamine Oxidase

A Multistate Empirical Valence Bond Description of Protonatable Amino Acids†

2006 ◽  
Vol 110 (2) ◽  
pp. 631-639 ◽  
Author(s):  
C. Mark Maupin ◽  
Kim F. Wong ◽  
Alexander V. Soudackov ◽  
Sun Kim ◽  
Gregory A. Voth
Keyword(s):  
Amino Acids ◽  
Valence Bond ◽  
Empirical Valence Bond
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