Molecular Modelling and Atomistic Insights into the Binding Mechanism of MmpL3 Mtb.
Mycobacterium Smegmatis
Mycobacterium tuberculosis
molecular docking
molecular dynamics simulations
mycobacterial membrane proteins large (MmpL3)
Journal
Chemistry & biodiversity
ISSN: 1612-1880
Titre abrégé: Chem Biodivers
Pays: Switzerland
ID NLM: 101197449
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
19
02
2022
accepted:
15
08
2022
pubmed:
16
8
2022
medline:
20
9
2022
entrez:
15
8
2022
Statut:
ppublish
Résumé
Mycobacterial membrane proteins Large (MmpLs), which belong to the resistance, nodulation, and division (RND) protein superfamily, play critical roles in transporting polymers, lipids, and immunomodulators. MmpLs have become one of the important therapeutic drug targets to emerge in recent times. In this study, two homology modelling techniques, Modeller and SWISS-MODEL, were used in modelling the three-dimensional protein structure of the MmpL3 of Mycobacterium tuberculosis using that of M. smegmatis as template. MmpL3 inhibitors, namely BM212, NITD304, SPIRO, and NITD349, in addition to the co-crystalized ligands AU1235, ICA38, SQ109 and rimonabant, were screened against the modelled structure and the Mmpl3 of M. smegmatis using molecular docking techniques. Protein-ligand interactions were analysed using molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann surface area computations. Novel residues Gln32, Leu165, Ile414, and Phe35 were identified as critical for binding to M. tuberculosis MmpL3, and conformational dynamics upon inhibitor binding were discussed.
Identifiants
pubmed: 35969844
doi: 10.1002/cbdv.202200160
doi:
Substances chimiques
Antitubercular Agents
0
Bacterial Proteins
0
Ligands
0
Membrane Proteins
0
Membrane Transport Proteins
0
Mycolic Acids
0
Polymers
0
Rimonabant
RML78EN3XE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202200160Subventions
Organisme : West African Center for Cell Biology of Infectious Pathogens, University of Ghana
Informations de copyright
© 2022 Wiley-VHCA AG, Zurich, Switzerland.
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