Gomez-Tamayo J.C.,Laboratori Of Medicina Computacional |
Cordomi A.,Laboratori Of Medicina Computacional |
Olivella M.,Departament Of Biologia Of Sistemesuniversitat Of Vic 08500Vic Spain |
Mayol E.,Laboratori Of Medicina Computacional |
And 2 more authors.
Protein Science | Year: 2016
The interactions of Met and Cys with other amino acid side chains have received little attention, in contrast to aromatic-aromatic, aromatic-aliphatic or/and aliphatic-aliphatic interactions. Precisely, these are the only amino acids that contain a sulfur atom, which is highly polarizable and, thus, likely to participate in strong Van der Waals interactions. Analysis of the interactions present in membrane protein crystal structures, together with the characterization of their strength in small-molecule model systems at the ab-initio level, predicts that Met-Met interactions are stronger than Met-Cys ≈ Met-Phe ≈ Cys-Phe interactions, stronger than Phe-Phe ≈ Phe-Leu interactions, stronger than the Met-Leu interaction, and stronger than Leu-Leu ≈ Cys-Leu interactions. These results show that sulfur-containing amino acids form stronger interactions than aromatic or aliphatic amino acids. Thus, these amino acids may provide additional driving forces for maintaining the 3D structure of membrane proteins and may provide functional specificity. © 2016 The Protein Society.
Deupi X.,Laboratori Of Medicina Computacional |
Olivella M.,Grup de Recerca en Bioinformatica i Estadistica Medica |
Sanz A.,Laboratori Of Medicina Computacional |
Dolker N.,Laboratori Of Medicina Computacional |
And 2 more authors.
Journal of Structural Biology | Year: 2010
In order to study the influence of Ser and Thr on the structure of transmembrane helices we have analyzed a database of helix stretches extracted from crystal structures of membrane proteins and an ensemble of model helices generated by molecular dynamics simulations. Both complementary analyses show that Ser and Thr in the g- conformation induce and/or stabilize a structural distortion in the helix backbone. Using quantum mechanical calculations, we have attributed this effect to the electrostatic repulsion between the side chain Oγ atom of Ser and Thr and the backbone carbonyl oxygen at position i - 3. In order to minimize the repulsive force between these negatively charged oxygens, there is a modest increase of the helix bend angle as well as a local opening of the helix turn preceding Ser/Thr. This small distortion can be amplified through the helix, resulting in a significant displacement of the residues located at the other side of the helix. The crystal structures of aquaporin Z and the β2-adrenergic receptor are used to illustrate these effects. Ser/Thr-induced structural distortions can be implicated in processes as diverse as ligand recognition, protein function and protein folding. © 2009 Elsevier Inc. All rights reserved.