| Title: | Structural and Affinity Determinants in the Interaction between Alcohol Acyltransferase from F. x ananassa and Several Alcohol Substrates: A Computational Study |
| Author(s): | Navarro-Retamal C; Gaete-Eastman C; Herrera R; Caballero J; Alzate-Morales JH; |
| Address: | "Centro de Bioinformatica y Simulacion Molecular, Facultad de Ingenieria, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile. Laboratorio de Fisiologia Vegetal y Genetica Molecular, Instituto de Ciencias Biologicas, Universidad de Talca, Casilla 747, Talca, Chile" |
| DOI: | 10.1371/journal.pone.0153057 |
| ISSN/ISBN: | 1932-6203 (Electronic) 1932-6203 (Linking) |
| Abstract: | "Aroma and flavor are important factors of fruit quality and consumer preference. The specific pattern of aroma is generated during ripening by the accumulation of volatiles compounds, which are mainly esters. Alcohol acyltransferase (AAT) (EC 2.3.1.84) catalyzes the esterification reaction of aliphatic and aromatic alcohols and acyl-CoA into esters in fruits and flowers. In Fragaria x ananassa, there are different volatiles compounds that are obtained from different alcohol precursors, where octanol and hexanol are the most abundant during fruit ripening. At present, there is not structural evidence about the mechanism used by the AAT to synthesize esters. Experimental data attribute the kinetic role of this enzyme to 2 amino acidic residues in a highly conserved motif (HXXXD) that is located in the middle of the protein. With the aim to understand the molecular and energetic aspects of volatiles compound production from F. x ananassa, we first studied the binding modes of a series of alcohols, and also different acyl-CoA substrates, in a molecular model of alcohol acyltransferase from Fragaria x ananassa (SAAT) using molecular docking. Afterwards, the dynamical behavior of both substrates, docked within the SAAT binding site, was studied using routine molecular dynamics (MD) simulations. In addition, in order to correlate the experimental and theoretical data obtained in our laboratories, binding free energy calculations were performed; which previous results suggested that octanol, followed by hexanol, presented the best affinity for SAAT. Finally, and concerning the SAAT molecular reaction mechanism, it is suggested from molecular dynamics simulations that the reaction mechanism may proceed through the formation of a ternary complex, in where the Histidine residue at the HXXXD motif deprotonates the alcohol substrates. Then, a nucleophilic attack occurs from alcohol charged oxygen atom to the carbon atom at carbonyl group of the acyl CoA. This mechanism is in agreement with previous results, obtained in our group, in alcohol acyltransferase from Vasconcellea pubescens (VpAAT1)" |
| Keywords: | Acyl Coenzyme A/chemistry/metabolism Acyltransferases/chemistry/genetics/*metabolism Alcohols/chemistry/*metabolism Amino Acid Motifs/genetics Amino Acid Sequence Binding Sites/genetics Esters/chemistry/metabolism Fragaria/*enzymology Molecular Docking Si; |
| Notes: | "MedlineNavarro-Retamal, Carlos Gaete-Eastman, Carlos Herrera, Raul Caballero, Julio Alzate-Morales, Jans H eng Research Support, Non-U.S. Gov't 2016/04/15 PLoS One. 2016 Apr 14; 11(4):e0153057. doi: 10.1371/journal.pone.0153057. eCollection 2016" |
