Effective way of modeling chemical catalysis: Empirical valence bond picture of role of solvent and catalyst in alkylation reactions

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.

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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

10.26434/chemrxiv.9547085.v1 ◽

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.

Download Full-text

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

10.26434/chemrxiv.9547085 ◽

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.

Download Full-text

Histidine protonation states are key in the LigI catalytic reaction mechanism

10.22541/au.161558380.06272745/v1 ◽

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.

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