Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family

Glucosylsucroses are potentially useful as additives in cosmetic and pharmaceutical formulations. Although enzymatic synthesis of glucosylsucroses is the most efficient method for their production, the key enzyme that produces them has remained unknown. Here, we report that glucosylsucrose synthase...

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Main Authors: Han Qiuyu, Yao Yuan, Liu Yuhan, Zhang Wenlu, Yu Jinyi, Na Heya, Liu Tianhao, Mayo Kevin H., Su Jiyong
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2022-04-01
Series:Acta Biochimica et Biophysica Sinica
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Online Access:https://www.sciengine.com/doi/10.3724/abbs.2022034
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author Han Qiuyu
Yao Yuan
Liu Yuhan
Zhang Wenlu
Yu Jinyi
Na Heya
Liu Tianhao
Mayo Kevin H.
Su Jiyong
author_facet Han Qiuyu
Yao Yuan
Liu Yuhan
Zhang Wenlu
Yu Jinyi
Na Heya
Liu Tianhao
Mayo Kevin H.
Su Jiyong
author_sort Han Qiuyu
collection DOAJ
description Glucosylsucroses are potentially useful as additives in cosmetic and pharmaceutical formulations. Although enzymatic synthesis of glucosylsucroses is the most efficient method for their production, the key enzyme that produces them has remained unknown. Here, we report that glucosylsucrose synthase from Thermosynechococcus elongatus (TeGSS) catalyzes the synthesis of glucosylsucrose using sucrose and UDP-glucose as substrates. These saccharides are homologous to glucosylsucroses produced by Nostoc sp. PCC 7120 (referred to as protein alr1000). When the ratio of UDP-glucose to sucrose is relatively high, TeGSS from cyanobacteria can hydrolyze excess UDP-glucose to UDP and glucose, indicating that sucrose provides a feedback mechanism for the control of glucosylsucrose synthesis. In the present study, we solved the crystal structure of TeGSS bound to UDP and sucrose. Our structure shows that the catalytic site contains a circular region that may allow glucosylsucroses with a right-hand helical structure to enter the catalytic site. Because active site residues Tyr18 and Arg179 are proximal to UDP and sucrose, we mutate these residues (i.e., Y18F and R179A) and show that they exhibit very low activity, supporting their role as catalytic groups. Overall, our study provides insight into the catalytic mechanism of TeGSS.
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publisher China Science Publishing & Media Ltd.
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series Acta Biochimica et Biophysica Sinica
spelling doaj-art-cdc729e43dfe47739c06f7bc2bf46d382025-08-20T01:52:15ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-04-015453754710.3724/abbs.202203420d259ccStructural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase familyHan Qiuyu0Yao Yuan1Liu Yuhan2Zhang Wenlu3Yu Jinyi4Na Heya5Liu Tianhao6Mayo Kevin H.7Su Jiyong8["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]["Media Academy, Jilin Engineering Normal University, Changchun 130052, China"]["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]["Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN 55455, USA"]["Engineering Research Center of Glycoconjugates Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun 130024, China"]Glucosylsucroses are potentially useful as additives in cosmetic and pharmaceutical formulations. Although enzymatic synthesis of glucosylsucroses is the most efficient method for their production, the key enzyme that produces them has remained unknown. Here, we report that glucosylsucrose synthase from Thermosynechococcus elongatus (TeGSS) catalyzes the synthesis of glucosylsucrose using sucrose and UDP-glucose as substrates. These saccharides are homologous to glucosylsucroses produced by Nostoc sp. PCC 7120 (referred to as protein alr1000). When the ratio of UDP-glucose to sucrose is relatively high, TeGSS from cyanobacteria can hydrolyze excess UDP-glucose to UDP and glucose, indicating that sucrose provides a feedback mechanism for the control of glucosylsucrose synthesis. In the present study, we solved the crystal structure of TeGSS bound to UDP and sucrose. Our structure shows that the catalytic site contains a circular region that may allow glucosylsucroses with a right-hand helical structure to enter the catalytic site. Because active site residues Tyr18 and Arg179 are proximal to UDP and sucrose, we mutate these residues (i.e., Y18F and R179A) and show that they exhibit very low activity, supporting their role as catalytic groups. Overall, our study provides insight into the catalytic mechanism of TeGSS.https://www.sciengine.com/doi/10.3724/abbs.2022034catalytic mechanismcrystal structureglucosylsucroseUDP-glucoseα-1,2-glucosyltransferase
spellingShingle Han Qiuyu
Yao Yuan
Liu Yuhan
Zhang Wenlu
Yu Jinyi
Na Heya
Liu Tianhao
Mayo Kevin H.
Su Jiyong
Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family
Acta Biochimica et Biophysica Sinica
catalytic mechanism
crystal structure
glucosylsucrose
UDP-glucose
α-1,2-glucosyltransferase
title Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family
title_full Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family
title_fullStr Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family
title_full_unstemmed Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family
title_short Structural basis for glucosylsucrose synthesis by a member of the α-1,2-glucosyltransferase family
title_sort structural basis for glucosylsucrose synthesis by a member of the α 1 2 glucosyltransferase family
topic catalytic mechanism
crystal structure
glucosylsucrose
UDP-glucose
α-1,2-glucosyltransferase
url https://www.sciengine.com/doi/10.3724/abbs.2022034
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