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Ligand Binding Sites02:40

Ligand Binding Sites

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
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Solvating Effects02:12

Solvating Effects

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An understanding of the solvating effect helps rationalize the relation between solvation and acidity of the compound. In addition, this also explains the relative stability of conjugate bases for compounds with different pKa values. This lesson details, in-depth, the principle of solvating effects. The strength of an acid and the stability of its corresponding conjugate base are determined using pKa values. This observed relationship is a consequence of solvation, which is the interaction...
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Predicting Products: Substitution vs. Elimination02:52

Predicting Products: Substitution vs. Elimination

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When a nucleophile and an alkyl halide react, nucleophilic substitution and β-elimination reactions compete to generate products.
The following factors can influence the mechanisms competing against each other:
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Predicting Products: SN1 vs. SN202:27

Predicting Products: SN1 vs. SN2

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Nucleophilic substitution reactions of alkyl halides can proceed via an SN1 or an SN2 mechanism. While in SN2 reactions, the nucleophile attacks the substrate simultaneously as the leaving group departs, in SN1 reactions, the substrate first dissociates to give the carbocation intermediate. Various factors such as the structure of the substrate, the strength of the nucleophile, and the nature of the solvent promote one mechanism over the other.
With increased substitution on the alkyl halide,...
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Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule02:17

Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule

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If a set of reactants can yield multiple constitutional isomers, but one of the isomers is obtained as the major product, the reaction is said to be regioselective. In such reactions, bond formation or breaking is favored at one reaction site over others.
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
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Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration02:34

Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration

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The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
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Related Experiment Video

Updated: Jul 14, 2025

Defining Substrate Specificities for Lipase and Phospholipase Candidates
08:59

Defining Substrate Specificities for Lipase and Phospholipase Candidates

Published on: November 23, 2016

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Electrostatic Interactions Dictate Bile Salt Hydrolase Substrate Preference.

Kien P Malarney1, Pamela V Chang2

  • 1Department of Microbiology, Cornell University, 930 Campus Road, Ithaca, NY 14853, United States.

Biorxiv : the Preprint Server for Biology
|October 9, 2023
PubMed
Summary
This summary is machine-generated.

Gut microbes modify bile acids, creating microbially-conjugated bile acids (MCBAs). A specific bile salt hydrolase (BSH) enzyme shows a unique preference for aromatic MCBAs, revealing a novel interaction mechanism.

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Area of Science:

  • Microbiology
  • Biochemistry
  • Metabolomics

Background:

  • The human gut microbiota significantly impacts host physiology through metabolite production and modification.
  • Bile acids, synthesized in the liver, are conjugated and secreted, then deconjugated by gut microbial bile salt hydrolases (BSHs).
  • A novel class of microbially-conjugated bile acids (MCBAs) involves alternative amino acid conjugations.

Approach:

  • Performed detailed kinetic studies to assess BSH enzyme preference for various bile acid conjugates.
  • Utilized molecular modeling and phylogenetic analyses to understand enzyme-substrate interactions.
  • Investigated the metabolic potential and enzymatic processing of MCBAs.

Key Points:

  • Identified a specific BSH enzyme exhibiting positive cooperativity exclusively for aromatic MCBAs.
  • Demonstrated that a substrate-specific cation-π interaction drives BSH preference for aromatic MCBAs.
  • Phylogenetic analysis suggests this interaction mechanism is prevalent among human gut microbial BSHs.

Conclusions:

  • Elucidated a novel mechanism of bile acid modification by gut microbes.
  • Highlighted the specific role of BSH enzymes in processing microbially-conjugated bile acids.
  • The findings suggest a widespread enzymatic strategy for modifying bile acids in the human gut microbiome.