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Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3

Capsaicinoids are phenolic compounds that have health benefits. However, the pungency and poor water solubility of these compounds limit their exploitation. Glycosylation is a powerful method to improve water solubility and reduce pungency while preserving bioactivity. PaGT3, a uridine diphosphate g...

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Autores principales: Maharjan, Rakesh, Fukuda, Yohta, Nakayama, Taisuke, Nakayama, Toru, Hamada, Hiroki, Ozaki, Shin-ichi, Inoue, Tsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900826/
https://www.ncbi.nlm.nih.gov/pubmed/35234151
http://dx.doi.org/10.1107/S2059798322000869
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author Maharjan, Rakesh
Fukuda, Yohta
Nakayama, Taisuke
Nakayama, Toru
Hamada, Hiroki
Ozaki, Shin-ichi
Inoue, Tsuyoshi
author_facet Maharjan, Rakesh
Fukuda, Yohta
Nakayama, Taisuke
Nakayama, Toru
Hamada, Hiroki
Ozaki, Shin-ichi
Inoue, Tsuyoshi
author_sort Maharjan, Rakesh
collection PubMed
description Capsaicinoids are phenolic compounds that have health benefits. However, the pungency and poor water solubility of these compounds limit their exploitation. Glycosylation is a powerful method to improve water solubility and reduce pungency while preserving bioactivity. PaGT3, a uridine diphosphate glycosyltransferase (UGT) from Phytolacca americana, is known for its ability to glycosylate capsaicinoids and other phenolic compounds. While structural information on several UGTs is available, structures of UGTs that can glycosylate a range of phenolic compounds are rare. To fill this gap, crystal structures of PaGT3 with a sugar-donor analogue (UDP-2-fluoroglucose) and the acceptors capsaicin and kaempferol were determined. PaGT3 adopts a GT-B-fold structure that is highly conserved among UGTs. However, the acceptor-binding pocket in PaGT3 is hydrophobic and large, and is surrounded by longer loops. The larger acceptor-binding pocket in PaGT3 allows the enzyme to bind a range of compounds, while the flexibility of the longer loops possibly plays a role in accommodating the acceptors in the binding pocket according to their shape and size. This structural information provides insights into the acceptor-binding mechanism in UGTs that bind multiple substrates.
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spelling pubmed-89008262022-03-29 Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3 Maharjan, Rakesh Fukuda, Yohta Nakayama, Taisuke Nakayama, Toru Hamada, Hiroki Ozaki, Shin-ichi Inoue, Tsuyoshi Acta Crystallogr D Struct Biol Research Papers Capsaicinoids are phenolic compounds that have health benefits. However, the pungency and poor water solubility of these compounds limit their exploitation. Glycosylation is a powerful method to improve water solubility and reduce pungency while preserving bioactivity. PaGT3, a uridine diphosphate glycosyltransferase (UGT) from Phytolacca americana, is known for its ability to glycosylate capsaicinoids and other phenolic compounds. While structural information on several UGTs is available, structures of UGTs that can glycosylate a range of phenolic compounds are rare. To fill this gap, crystal structures of PaGT3 with a sugar-donor analogue (UDP-2-fluoroglucose) and the acceptors capsaicin and kaempferol were determined. PaGT3 adopts a GT-B-fold structure that is highly conserved among UGTs. However, the acceptor-binding pocket in PaGT3 is hydrophobic and large, and is surrounded by longer loops. The larger acceptor-binding pocket in PaGT3 allows the enzyme to bind a range of compounds, while the flexibility of the longer loops possibly plays a role in accommodating the acceptors in the binding pocket according to their shape and size. This structural information provides insights into the acceptor-binding mechanism in UGTs that bind multiple substrates. International Union of Crystallography 2022-02-21 /pmc/articles/PMC8900826/ /pubmed/35234151 http://dx.doi.org/10.1107/S2059798322000869 Text en © Rakesh Maharjan et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
spellingShingle Research Papers
Maharjan, Rakesh
Fukuda, Yohta
Nakayama, Taisuke
Nakayama, Toru
Hamada, Hiroki
Ozaki, Shin-ichi
Inoue, Tsuyoshi
Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
title Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
title_full Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
title_fullStr Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
title_full_unstemmed Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
title_short Structural basis for substrate recognition in the Phytolacca americana glycosyltransferase PaGT3
title_sort structural basis for substrate recognition in the phytolacca americana glycosyltransferase pagt3
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900826/
https://www.ncbi.nlm.nih.gov/pubmed/35234151
http://dx.doi.org/10.1107/S2059798322000869
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