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Histidine protonation states are key in the LigI catalytic reaction mechanism
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  • LINA ZHAO,
  • Dibyendu Mondal,
  • Weifeng Li,
  • Yuguang Mu,
  • Philipp Kaldis
LINA ZHAO
Lund University
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Dibyendu Mondal
University of California San Francisco
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Weifeng Li
Shandong University
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Yuguang Mu
Nanyang Technological University
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Philipp Kaldis
Lund University
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Abstract

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.

Peer review status:IN REVISION

17 Feb 2021Submitted to PROTEINS: Structure, Function, and Bioinformatics
19 Feb 2021Assigned to Editor
19 Feb 2021Submission Checks Completed
12 Mar 2021Reviewer(s) Assigned
30 Mar 2021Review(s) Completed, Editorial Evaluation Pending
31 Mar 2021Editorial Decision: Revise Major