Enzymatic reaction mechanism of cis-aconitate decarboxylase based on the crystal structure of IRG1 from Bacillus subtilis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
received:
05
05
2020
accepted:
22
06
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
1
1
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32647315
doi: 10.1038/s41598-020-68419-y
pii: 10.1038/s41598-020-68419-y
pmc: PMC7347537
doi:
Substances chimiques
Bacterial Proteins
0
Aconitic Acid
93371T1BXP
Carboxy-Lyases
EC 4.1.1.-
aconitate decarboxylase
EC 4.1.1.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11305Références
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