The three-dimensional structures of the adenylation domains (A) of eight modules of SyrE, a peptide synthetase involved in the biosynthesis of syringomycin, was investigated by homology modeling using as a template the adenylation domain of gramicidin synthetase 1. Multiple sequence alignment of the adenylation domains of each of the eight modules of SyrE, allowed to identify the residues which delimitate the active site pockets. The active sites of the A domains of SyrE1 and SyrE2, involved in the insertion of the two serine residues in syringomycin, are essentially equivalent. The docking of these models with L-Ser and D-Ser showed that L-Ser is preferred as a substrate on the basis of stabilizing interactions. This is in accordance with previously shown stereo-specificity of these modules. Analogous investigation carried out on the modules SyrE3 and SyrE4 showed the preference for the L-isomer of their substrate, 2,4-diaminobutyric acid. In addition, the model of SyrE8, whose substrate amino acid is arginine, allowed to evidence specificity - conferring residues for this residue, which had not been previously reported.
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