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Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference

The human intestines are colonized by trillions of microbes, comprising the gut microbiota, which produce diverse small molecule metabolites and modify host metabolites, such as bile acids, that regulate host physiology. Biosynthesized in the liver, bile acids are conjugated with glycine or taurine...

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Autores principales: Malarney, Kien P., Chang, Pamela V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557579/
https://www.ncbi.nlm.nih.gov/pubmed/37808785
http://dx.doi.org/10.1101/2023.09.25.559308
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author Malarney, Kien P.
Chang, Pamela V.
author_facet Malarney, Kien P.
Chang, Pamela V.
author_sort Malarney, Kien P.
collection PubMed
description The human intestines are colonized by trillions of microbes, comprising the gut microbiota, which produce diverse small molecule metabolites and modify host metabolites, such as bile acids, that regulate host physiology. Biosynthesized in the liver, bile acids are conjugated with glycine or taurine and secreted into the intestines, where gut microbial bile salt hydrolases (BSHs) deconjugate the amino acid to produce unconjugated bile acids that serve as precursors for secondary bile acid metabolites. Among these include a recently discovered class of microbially-conjugated bile acids (MCBAs), wherein alternative amino acids are conjugated onto bile acids. To elucidate the metabolic potential of MCBAs, we performed detailed kinetic studies to investigate the preference of BSHs for host- and microbially-conjugated bile acids. We identified a BSH that exhibits positive cooperativity uniquely for MCBAs containing an aromatic sidechain. Further molecular modeling and phylogenetic analyses indicated that BSH preference for aromatic MCBAs is due to a substrate-specific cation-π interaction and is predicted to be widespread among human gut microbial BSHs.
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spelling pubmed-105575792023-10-07 Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference Malarney, Kien P. Chang, Pamela V. bioRxiv Article The human intestines are colonized by trillions of microbes, comprising the gut microbiota, which produce diverse small molecule metabolites and modify host metabolites, such as bile acids, that regulate host physiology. Biosynthesized in the liver, bile acids are conjugated with glycine or taurine and secreted into the intestines, where gut microbial bile salt hydrolases (BSHs) deconjugate the amino acid to produce unconjugated bile acids that serve as precursors for secondary bile acid metabolites. Among these include a recently discovered class of microbially-conjugated bile acids (MCBAs), wherein alternative amino acids are conjugated onto bile acids. To elucidate the metabolic potential of MCBAs, we performed detailed kinetic studies to investigate the preference of BSHs for host- and microbially-conjugated bile acids. We identified a BSH that exhibits positive cooperativity uniquely for MCBAs containing an aromatic sidechain. Further molecular modeling and phylogenetic analyses indicated that BSH preference for aromatic MCBAs is due to a substrate-specific cation-π interaction and is predicted to be widespread among human gut microbial BSHs. Cold Spring Harbor Laboratory 2023-09-26 /pmc/articles/PMC10557579/ /pubmed/37808785 http://dx.doi.org/10.1101/2023.09.25.559308 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Malarney, Kien P.
Chang, Pamela V.
Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
title Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
title_full Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
title_fullStr Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
title_full_unstemmed Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
title_short Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference
title_sort electrostatic interactions dictate bile salt hydrolase substrate preference
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557579/
https://www.ncbi.nlm.nih.gov/pubmed/37808785
http://dx.doi.org/10.1101/2023.09.25.559308
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