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Article

Structural Insights into the Substrate Transport Mechanisms in GTR Transporters through Ensemble Docking

1
Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Llano Subercaseaux 2801-piso 6, Santiago 8900000, Chile
2
DynaMo Center, Department of Plant and Environmental Sciences, University of Copenhagen, 1871 Frederiksberg, Denmark
3
Center for Bioinformatics, Simulation and Modeling (CBSM), Faculty of Engineering, Campus Talca, Universidad de Talca, 1 Poniente No. 1141, Casilla 721, Talca 3460000, Chile
4
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
5
Research Center for the Development of Novel Therapeutic Alternatives for Alcohol Use Disorders, Santiago 8900000, Chile
*
Author to whom correspondence should be addressed.
Academic Editor: Istvan Simon
Int. J. Mol. Sci. 2022, 23(3), 1595; https://doi.org/10.3390/ijms23031595
Received: 5 January 2022 / Revised: 11 January 2022 / Accepted: 19 January 2022 / Published: 29 January 2022
(This article belongs to the Special Issue Applied and Advanced Research in Plant Bioinformatics)
Glucosinolate transporters (GTRs) are part of the nitrate/peptide transporter (NPF) family, members of which also transport specialized secondary metabolites as substrates. Glucosinolates are defense compounds derived from amino acids. We selected 4-methylthiobutyl (4MTB) and indol-3-ylmethyl (I3M) glucosinolates to study how GTR1 from Arabidopsis thaliana transports these substrates in computational simulation approaches. The designed pipeline reported here includes massive docking of 4MTB and I3M in an ensemble of GTR1 conformations (in both inward and outward conformations) extracted from molecular dynamics simulations, followed by clustered and substrate–protein interactions profiling. The identified key residues were mutated, and their role in substrate transport was tested. We were able to identify key residues that integrate a major binding site of these substrates, which is critical for transport activity. In silico approaches employed here represent a breakthrough in the plant transportomics field, as the identification of key residues usually takes a long time if performed from a purely wet-lab experimental perspective. The inclusion of structural bioinformatics in the analyses of plant transporters significantly speeds up the knowledge-gaining process and optimizes valuable time and resources. View Full-Text
Keywords: glucosinolates; GTRs; ensemble docking; phytocompounds transport mechanism; membrane protein modeling glucosinolates; GTRs; ensemble docking; phytocompounds transport mechanism; membrane protein modeling
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MDPI and ACS Style

Peña-Varas, C.; Kanstrup, C.; Vergara-Jaque, A.; González-Avendaño, M.; Crocoll, C.; Mirza, O.; Dreyer, I.; Nour-Eldin, H.; Ramírez, D. Structural Insights into the Substrate Transport Mechanisms in GTR Transporters through Ensemble Docking. Int. J. Mol. Sci. 2022, 23, 1595. https://doi.org/10.3390/ijms23031595

AMA Style

Peña-Varas C, Kanstrup C, Vergara-Jaque A, González-Avendaño M, Crocoll C, Mirza O, Dreyer I, Nour-Eldin H, Ramírez D. Structural Insights into the Substrate Transport Mechanisms in GTR Transporters through Ensemble Docking. International Journal of Molecular Sciences. 2022; 23(3):1595. https://doi.org/10.3390/ijms23031595

Chicago/Turabian Style

Peña-Varas, Carlos, Christa Kanstrup, Ariela Vergara-Jaque, Mariela González-Avendaño, Christoph Crocoll, Osman Mirza, Ingo Dreyer, Hussam Nour-Eldin, and David Ramírez. 2022. "Structural Insights into the Substrate Transport Mechanisms in GTR Transporters through Ensemble Docking" International Journal of Molecular Sciences 23, no. 3: 1595. https://doi.org/10.3390/ijms23031595

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