Loop-to-helix transition in the structure of multidrug regulator AcrR at the entrance of the drug-binding cavity
Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56Å resolutio...
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Published in | Journal of structural biology Vol. 194; no. 1; pp. 18 - 28 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.04.2016
Elseiver |
Subjects | |
Online Access | Get full text |
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Summary: | Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices α4 and α7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helix α4 is stabilized by the hydrogen bond between Glu67 (helix α4) and Gln130 (helix α7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix α4. This local conformational switch of helix α4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution small-molecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AC02-06CH11357 USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23) National Institutes of Health (NIH). National Institute of Allergy and Infectious Diseases (NIAID) |
ISSN: | 1047-8477 1095-8657 |
DOI: | 10.1016/j.jsb.2016.01.008 |