Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis

Abstract Itaconate, which is formed by decarboxylation of cis-aconitate—an intermediate metabolite in the tricarboxylic acid cycle—has been used as a building block in polymer synthesis and is an important chemical in several biomedical and industrial applications. Itaconate is an immunometabolite w...

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Autores principales:	Hye Lin Chun, So Yeon Lee, Sung Hoon Lee, Chang Sup Lee, Hyun Ho Park
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4739c9d502745f1960131aee2ed3040
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spelling	oai:doaj.org-article:a4739c9d502745f1960131aee2ed30402021-12-02T16:24:49ZEnzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis10.1038/s41598-020-68419-y2045-2322https://doaj.org/article/a4739c9d502745f1960131aee2ed30402020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68419-yhttps://doaj.org/toc/2045-2322Abstract Itaconate, which is formed by decarboxylation of cis-aconitate—an intermediate metabolite in the tricarboxylic acid cycle—has been used as a building block in polymer synthesis and is an important chemical in several biomedical and industrial applications. Itaconate is an immunometabolite with antibacterial, antiviral, immunoregulatory, and tumor-promoting activities. Recent focus has been on the role of itaconate in the field of immunology, with immune-responsive gene 1 (IRG1) being identified as the cis-aconitate decarboxylase responsible for itaconate production. We solved the structure of IRG1 from Bacillus subtilis (bsIRG1) and showed that IRG1 adopts either a closed or an open conformation; bsIRG1 was in the open form. A1 and A2 loops around the active site are flexible and can control the formation of the open and closed forms of IRG1. An in silico docking simulation showed that only the open form of IRG1 can accommodate the substrate. The most energetically favorable position of cis-aconitate in the active site of bsIRG1 involved the localization of C2 and C5 of cis-aconitate into the H102 region and H151 region of bsIRG1, respectively. Based on the structural study of bsIRG1, compared with IDS epimerase, and in silico docking simulation, we proposed two tentative enzymatic reaction mechanisms of IRG1, a two-base model and a one-base model.Hye Lin ChunSo Yeon LeeSung Hoon LeeChang Sup LeeHyun Ho ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hye Lin Chun So Yeon Lee Sung Hoon Lee Chang Sup Lee Hyun Ho Park Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis
description	Abstract Itaconate, which is formed by decarboxylation of cis-aconitate—an intermediate metabolite in the tricarboxylic acid cycle—has been used as a building block in polymer synthesis and is an important chemical in several biomedical and industrial applications. Itaconate is an immunometabolite with antibacterial, antiviral, immunoregulatory, and tumor-promoting activities. Recent focus has been on the role of itaconate in the field of immunology, with immune-responsive gene 1 (IRG1) being identified as the cis-aconitate decarboxylase responsible for itaconate production. We solved the structure of IRG1 from Bacillus subtilis (bsIRG1) and showed that IRG1 adopts either a closed or an open conformation; bsIRG1 was in the open form. A1 and A2 loops around the active site are flexible and can control the formation of the open and closed forms of IRG1. An in silico docking simulation showed that only the open form of IRG1 can accommodate the substrate. The most energetically favorable position of cis-aconitate in the active site of bsIRG1 involved the localization of C2 and C5 of cis-aconitate into the H102 region and H151 region of bsIRG1, respectively. Based on the structural study of bsIRG1, compared with IDS epimerase, and in silico docking simulation, we proposed two tentative enzymatic reaction mechanisms of IRG1, a two-base model and a one-base model.
format	article
author	Hye Lin Chun So Yeon Lee Sung Hoon Lee Chang Sup Lee Hyun Ho Park
author_facet	Hye Lin Chun So Yeon Lee Sung Hoon Lee Chang Sup Lee Hyun Ho Park
author_sort	Hye Lin Chun
title	Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis
title_short	Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis
title_full	Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis
title_fullStr	Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis
title_full_unstemmed	Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis
title_sort	enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of irg1 from bacillus subtilis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/a4739c9d502745f1960131aee2ed3040
work_keys_str_mv	AT hyelinchun enzymaticreactionmechanismofcisaconitatedecarboxylasebasedonthecrystalstructureofirg1frombacillussubtilis AT soyeonlee enzymaticreactionmechanismofcisaconitatedecarboxylasebasedonthecrystalstructureofirg1frombacillussubtilis AT sunghoonlee enzymaticreactionmechanismofcisaconitatedecarboxylasebasedonthecrystalstructureofirg1frombacillussubtilis AT changsuplee enzymaticreactionmechanismofcisaconitatedecarboxylasebasedonthecrystalstructureofirg1frombacillussubtilis AT hyunhopark enzymaticreactionmechanismofcisaconitatedecarboxylasebasedonthecrystalstructureofirg1frombacillussubtilis
_version_	1718384128195297280

Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis

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