Charge is Major Determinant of Activation of the Ligand-Responsive Multidrug Resistance Gene Regulator, BmrR
| Autor: | Bryan Kohrs, Sharrol Bachas, Herschel Wade |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Transcriptional Activation
0301 basic medicine Stereochemistry Allosteric regulation Regulator Ligands Biochemistry 03 medical and health sciences Molecular recognition Allosteric Regulation Bacterial Proteins Drug Discovery Escherichia coli Transcriptional regulation General Pharmacology Toxicology and Pharmaceutics Pharmacology 030102 biochemistry & molecular biology biology Membrane transport protein Ligand Organic Chemistry Membrane Transport Proteins Anti-Bacterial Agents 030104 developmental biology biology.protein Molecular Medicine Signal transduction Selectivity Bacillus subtilis |
| Zdroj: | ChemMedChem. 11:1038-1041 |
| ISSN: | 1860-7179 |
| DOI: | 10.1002/cmdc.201600059 |
| Popis: | A medium-throughput approach (80+ compounds) to investigate allosteric transcriptional control in the multidrug resistance gene regulator BmrR, with cations, zwitterions, uncharged compounds and anions, is described. Even at the allosteric level, BmrR is quite promiscuous with regard to molecular shape and structure, but it is sensitive to molecular charge. A role for charge is further supported by differences in the activation properties of structurally similar ligands displaying variable charge properties as well as differences in activation by zwitterions and uncharged ligands, which show similar binding affinities. A comparison of allosteric selectivity with the distribution of differently charged ligands in bacterial cellular environments suggests that the selectivity of charge is a major factor in discrimination of xenobiotics, and native biological compounds and metabolites. Interestingly, in eukaryotic cells, the selectivity of cationic ligands might be a protective mechanism against chemical agents that act in a promiscuous fashion. |
| Databáze: | OpenAIRE |
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