Characterization of substrate specificity and inhibitory mechanism of bile salt hydrolase from Lactobacillus reuteri CRL 1098 using molecular docking analysis
Autor: | Ana Estela Ledesma, Ana Yanina Bustos, María Pía Taranto |
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Rok vydání: | 2021 |
Předmět: |
0106 biological sciences
0301 basic medicine chemistry.chemical_classification biology Chemistry Substrate (chemistry) Bioengineering General Medicine biology.organism_classification Ascorbic acid 01 natural sciences Applied Microbiology and Biotechnology Lactobacillus reuteri 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology Enzyme Biochemistry Docking (molecular) 010608 biotechnology Binding site Caffeic acid phenethyl ester Citric acid Biotechnology |
Zdroj: | Biotechnology Letters. 43:1063-1073 |
ISSN: | 1573-6776 0141-5492 |
Popis: | To elucidate the molecular mechanisms involved in the substrate interaction of the bile salt hydrolase of Lactobacillus reuteri CRL 1098 (LrBSH) with bile acids (BAs) and to evaluate potential enzyme inhibitors based on computer and in vitro modeling assays. Asp19, Asn79, and Asn171 participated in the LrBSH interaction with all BAs tested while Leu56 and Glu 222 played an important role in the interaction with glyco- and tauro-conjugated BAs, respectively. A great percentage of hydrophobic and polar interactions were responsible for the binding of LrBSH with glyco- and tauro-conjugated BAs, respectively. Remarkably, the four binding pocket loops participated in the substrate binding site of LrBSH unlike most of the reported BSHs. Inhibition assays showed that ascorbic acid, citric acid, penicillin G, and ciprofloxacin decreased LrBSH activity by 47.1%, 40.14%, 28.8%, and 9%, respectively. Docking analysis revealed that tetracycline and caffeic acid phenethyl ester had the low binding energy (−7.32 and −7.19 kcal/mol, respectively) and resembled the interaction pattern of GDCA (−6.88 kcal/mol) while penicillin (−6.25 kcal/mol) and ascorbic acid (−5.98 kcal/mol) interacted at a longer distance. This study helps to delve into the molecular mechanisms involved in the recognition of substrates and potential inhibitors of LrBSH. |
Databáze: | OpenAIRE |
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