INVESTIGADORES
BUSTOS Ana Yanina
artículos
Título:
Characterization of substrate specificity and inhibitory mechanism of bile salt hydrolasehydrolase from Lactobacillus reuteri CRL 1098 using molecular docking analysis
Autor/es:
LEDESMA, AE; TARANTO, M. P.; BUSTOS, A. Y., CORRESPONDING AUTHOR
Revista:
BIOTECHNOLOGY LETTERS
Editorial:
SPRINGER
Referencias:
Año: 2021
ISSN:
0141-5492
Resumen:
Objectives: The bile salt hydrolase of Lactobacillus reuteri CRL 1098 (LrBSH) was modeled, and molecular docking analysis was performed to study the molecular mechanisms involved in the substrate recognition of the enzyme with six bile acids (BAs) and two potential inhibitors of the enzyme such as caffeic acid phenethyl ester and penicillin. Besides, in silico site-directed mutants were constructed to study the role of key residues in LrBSH substrate preference. Results: We found that Asp19, Asn79, and Asn171 participate in the LrBSH interaction with all BAs tested. Also, a greater percentage of hydrophobic interactions with Leu18, Leu24, Leu56, Ala135 and Ala136, and polar and ionic interactions with Ser221, Asn172, and Glu222 residues in the binding site of LrBSH were predicted for glyco- and tauro-conjugated BAs, respectively. Remarkably, the four binding pocket loops identified participate in the substrate binding site of LrBSH unlike most of the reported BSHs. In silico mutants showed that Leu56 and Glu 222 play an important role in the interaction of LrBSH with glyco- and tauro-conjugated BAs, respectively. In relation to the two inhibitors studied, our results revealed that both compounds resemble the interaction pattern of GDCA with LrBSH close to Cys2 residue, suggesting that they could act as potential enzyme inhibitors.Conclusion: This study helps us to delve into the molecular mechanisms involved in the recognition of substrates and potential inhibitors by LrBSH and could be extrapolated to several fields related to enzymatic engineering.