Demystifying the catalytic pathway of Mycobacterium tuberculosis isocitrate lyase.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 11 2020
03 11 2020
Historique:
received:
08
04
2020
accepted:
07
10
2020
entrez:
4
11
2020
pubmed:
5
11
2020
medline:
10
3
2021
Statut:
epublish
Résumé
Pulmonary tuberculosis, caused by Mycobacterium tuberculosis, is one of the most persistent diseases leading to death in humans. As one of the key targets during the latent/dormant stage of M. tuberculosis, isocitrate lyase (ICL) has been a subject of interest for new tuberculosis therapeutics. In this work, the cleavage of the isocitrate by M. tuberculosis ICL was studied using quantum mechanics/molecular mechanics method at M06-2X/6-31+G(d,p): AMBER level of theory. The electronic embedding approach was applied to provide a better depiction of electrostatic interactions between MM and QM regions. Two possible pathways (pathway I that involves Asp108 and pathway II that involves Glu182) that could lead to the metabolism of isocitrate was studied in this study. The results suggested that the core residues involved in isocitrate catalytic cleavage mechanism are Asp108, Cys191 and Arg228. A water molecule bonded to Mg
Identifiants
pubmed: 33144641
doi: 10.1038/s41598-020-75799-8
pii: 10.1038/s41598-020-75799-8
pmc: PMC7609661
doi:
Substances chimiques
Bacterial Proteins
0
Isocitrates
0
Glutamine
0RH81L854J
Asparagine
7006-34-0
isocitric acid
9RW6G5D4MQ
icl protein, Mycobacterium
EC 4.1.3.-
Isocitrate Lyase
EC 4.1.3.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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