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Histidine protonation states are key in the LigI catalytic reaction mechanism

Zhao, Lina LU ; Mondal, Dibyendu ; Li, Weifeng ; Mu, Yuguang and Kaldis, Philipp LU orcid (2022) In Proteins 90(1). p.123-130
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... (More)

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 &ip.eop; site, however, protonation at the δ site may be favored during specific steps of the 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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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Proteins
volume
90
issue
1
pages
123 - 130
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85112672570
  • pmid:34318530
ISSN
0887-3585
DOI
10.1002/prot.26191
language
English
LU publication?
yes
id
0684bf80-c7f1-4407-8829-f77a70398fbc
date added to LUP
2021-08-02 11:05:55
date last changed
2024-12-15 09:36:28
@article{0684bf80-c7f1-4407-8829-f77a70398fbc,
  abstract     = {{<p>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 &amp;ip.eop; site, however, protonation at the δ site may be favored during specific steps of the 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.<br/></p>}},
  author       = {{Zhao, Lina and Mondal, Dibyendu and Li, Weifeng and Mu, Yuguang and Kaldis, Philipp}},
  issn         = {{0887-3585}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{123--130}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Proteins}},
  title        = {{Histidine protonation states are key in the LigI catalytic reaction mechanism}},
  url          = {{http://dx.doi.org/10.1002/prot.26191}},
  doi          = {{10.1002/prot.26191}},
  volume       = {{90}},
  year         = {{2022}},
}