title: Molecular insights into quorum sensing in Acidithiobacillus ferrooxidans bacteria via molecular modelling of the transcriptional regulator AfeR and of the binding mode of long-chain acyl homoserine lactones.
abstract: Amino acid sequence alignments of the transcriptional regulator AfeR, which is involved in type 1 quorum sensing (QS) in Acidithiobacillus ferrooxidans bacteria, with other acyl homoserine lactone (AHL)-dependent QS regulators, revealed the presence of strictly or highly conserved residues located in the active site of these proteins. As a consequence, a model of AfeR was constructed to study the binding mode of long-chain AHLs using molecular dynamics and subsequent rigid ligand docking. This study, performed on the tetradecanoyl homoserine lactone C14-AHL, showed that the binding mode involved a curved conformation. Based on these results, the binding mode of tetradec-7-Z enoyl homoserine lactone, an AHL that is conformationally constrained due to the presence of the cis double bond, was investigated. This mono-unsaturated AHL with its preferential curved shape conformation was found to be particularly well adapted to the active site of AfeR. These results should be helpful in the rational design of QS modulators with potential biotechnological applications and especially in the improvement of industrial bioleaching from ores.
authors.affiliation: Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique, INSA Lyon, Bât J. Verne, 20 av A. Einstein, 69621, Villeurbanne Cedex, France. laurent.soulere@insa-lyon.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Soulère
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guiliani
authors.forename: Yves
authors.initials: Y
authors.lastname: Queneau
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Jerez
authors.forename: Alain
authors.initials: A
authors.lastname: Doutheau
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D042763:Acidithiobacillus / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D053038:Quorum Sensing; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; C088386:homoserine lactone; D015107:4-Butyrolactone