Conformational dynamics of L-lysine, L-arginine, L-ornithine binding protein reveals ligand-dependent plasticity

Authors

  • Daniel-Adriano Silva,

    1. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, D.F. C.P. 04510, México
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  • Lenin Domínguez-Ramírez,

    1. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, D.F. C.P. 04510, México
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    • Department of Molecular and Cellular Biology, College of Biological Sciences, University of California at Davis, CA 95616, USA

  • Arturo Rojo-Domínguez,

    1. Division de Ciencias Naturales e Ingeniería, Universidad Autónoma Metropolitana-Unidad Cuajimalpa, C.P. 11950, México, D.F
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  • Alejandro Sosa-Peinado

    Corresponding author
    1. Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, D.F. C.P. 04510, México
    • Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, C.P. 04510, México, D.F
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Abstract

The molecular basis of multiple ligand binding affinity for amino acids in periplasmic binding proteins (PBPs) and in the homologous domain for class C G-protein coupled receptors is an unsolved question. Here, using unrestrained molecular dynamic simulations, we studied the ligand binding mechanism present in the L-lysine, L-arginine, L-ornithine binding protein. We developed an analysis based on dihedral angles for the description of the conformational changes upon ligand binding. This analysis has an excellent correlation with each of the two main movements described by principal component analysis (PCA) and it's more convenient than RMSD measurements to describe the differences in the conformational ensembles observed. Furthermore, an analysis of hydrogen bonds showed specific interactions for each ligand studied as well as the ligand interaction with the aromatic residues Tyr-14 and Phe-52. Using uncharged histidine tautomers, these interactions are not observed. On the basis of these results, we propose a model in which hydrogen bond interactions place the ligand in the correct orientation to induce a cation–π interaction with Tyr-14 and Phe-52 thereby stabilizing the closed state. Our results also show that this protein adopts slightly different closed conformations to make available specific hydrogen bond interactions for each ligand thus, allowing a single mechanism to attain multiple ligand specificity. These results shed light on the experimental evidence for ligand-dependent conformational plasticity not explained by the previous crystallographic data. Proteins 2011. © 2011 Wiley-Liss, Inc.

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