CONICET | Buscador de Institutos y Recursos Humanos

The microbial enzyme Bile Salt Hydrolase (BSH) releases free BA plus amino acid(taurine or glycine) from the Conjugated Bile Acids (BA). Currently, BSH inhibitorsmay become novel and attractive growth promoters. Detailed knowledge of BSHsubstrate preferences provide a solid foundation for rationally BSH inhibitordesign.The aim of this work was to characterize the substrate specificity of BSH fromLactobacillus reuteri CRL 1098 using molecular docking analysis and DFTcalculations. The deconjugation of both taurocholate and glycocholate optimizedfrom Gaussian Program, was performed using AutoDock 4.2 tool with asemiempirical free-energy force.Our results showed that CRL 1098-BSH exhibited greater hydrolysis toward glyco-conjugated BA compared to tauro-conjugated ones. In fact, the molecular dockingillustrated that both conjugated are embedded into binding pockets with thebinding energy (BE) of ?7.31 and -5.72 kcal/mol, respectively, indicating anenergetically favorable binding for glycoholate as compared to taurocholate.In addition, docking results indicate a polar or charged nature of the residues inthe binding site in accordance with the five catalytically important amino acidsresidues (Cys, Asp, Asn, Asn, Arg) are highly conserved in CRL 1098 strain.Hydrogen bonding interaction can be observed between these residues withinboth taurocholate and glycocholate. The formation of less hydrogen bonds wasobserved in the interactions of taurocholate with BSH as compared toglycocholate, reflecting a lesser binding affinity between the ligand and receptor.All these correlated well with experimental data of glycocholate being morefavorable to bind with BSH as compared to taurocholate.In this work we provide the molecular basis for substrate recognition of BSH fromthe probiotic CRL 1098 strain. These data could be useful for development of safeand cost effective BSH inhibitors as a replacement of current antibiotic growthpromoters.