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Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH
In this work, we have investigated the binding conformations of the substrate in the active site of 5-HIU hydrolase kpHIUH and its catalytic hydrolysis mechanism. Docking calculations revealed that the substrate adopts a conformation in the active site with its molecular plane laying parallel to the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272043/ https://www.ncbi.nlm.nih.gov/pubmed/34202153 http://dx.doi.org/10.3390/molecules26133884 |
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author | Wang, Xixi Shan, Jiankai Liu, Wei Li, Jing Tan, Hongwei Li, Xichen Chen, Guangju |
author_facet | Wang, Xixi Shan, Jiankai Liu, Wei Li, Jing Tan, Hongwei Li, Xichen Chen, Guangju |
author_sort | Wang, Xixi |
collection | PubMed |
description | In this work, we have investigated the binding conformations of the substrate in the active site of 5-HIU hydrolase kpHIUH and its catalytic hydrolysis mechanism. Docking calculations revealed that the substrate adopts a conformation in the active site with its molecular plane laying parallel to the binding interface of the protein dimer of kpHIUH, in which His7 and His92 are located adjacent to the hydrolysis site C6 and have hydrogen bond interactions with the lytic water. Based on this binding conformation, density functional theory calculations indicated that the optimal catalytic mechanism consists of two stages: (1) the lytic water molecule is deprotonated by His92 and carries out nucleophilic attack on C6=O of 5-HIU, resulting in an oxyanion intermediate; (2) by accepting a proton transferred from His92, C6–N5 bond is cleaved to completes the catalytic cycle. The roles of His7, His92, Ser108 and Arg49 in the catalytic reaction were revealed and discussed in detail. |
format | Online Article Text |
id | pubmed-8272043 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82720432021-07-11 Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH Wang, Xixi Shan, Jiankai Liu, Wei Li, Jing Tan, Hongwei Li, Xichen Chen, Guangju Molecules Article In this work, we have investigated the binding conformations of the substrate in the active site of 5-HIU hydrolase kpHIUH and its catalytic hydrolysis mechanism. Docking calculations revealed that the substrate adopts a conformation in the active site with its molecular plane laying parallel to the binding interface of the protein dimer of kpHIUH, in which His7 and His92 are located adjacent to the hydrolysis site C6 and have hydrogen bond interactions with the lytic water. Based on this binding conformation, density functional theory calculations indicated that the optimal catalytic mechanism consists of two stages: (1) the lytic water molecule is deprotonated by His92 and carries out nucleophilic attack on C6=O of 5-HIU, resulting in an oxyanion intermediate; (2) by accepting a proton transferred from His92, C6–N5 bond is cleaved to completes the catalytic cycle. The roles of His7, His92, Ser108 and Arg49 in the catalytic reaction were revealed and discussed in detail. MDPI 2021-06-25 /pmc/articles/PMC8272043/ /pubmed/34202153 http://dx.doi.org/10.3390/molecules26133884 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Xixi Shan, Jiankai Liu, Wei Li, Jing Tan, Hongwei Li, Xichen Chen, Guangju Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH |
title | Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH |
title_full | Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH |
title_fullStr | Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH |
title_full_unstemmed | Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH |
title_short | Theoretical Studies on the Binding Mode and Reaction Mechanism of TLP Hydrolase kpHIUH |
title_sort | theoretical studies on the binding mode and reaction mechanism of tlp hydrolase kphiuh |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272043/ https://www.ncbi.nlm.nih.gov/pubmed/34202153 http://dx.doi.org/10.3390/molecules26133884 |
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