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Title: How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator

Abstract

Bacterial catabolism of aromatic compounds from various sources including phenylpropanoids and flavonoids that are abundant in soil plays an important role in the recycling of carbon in the ecosystem. We have determined the crystal structures of apo-HcaR from Acinetobacter sp. ADP1, a MarR/SlyA transcription factor, in complexes with hydroxycinnamates and a specific DNA operator. The protein regulates the expression of the hca catabolic operon in Acinetobacter and related bacterial strains, allowing utilization of hydroxycinnamates as sole sources of carbon. HcaR binds multiple ligands, and as a result the transcription of genes encoding several catabolic enzymes is increased. The 1.9-2.4 Å resolution structures presented here explain how HcaR recognizes four ligands (ferulate, 3,4-dihydroxybenzoate, p-coumarate, and vanillin) using the same binding site. The ligand promiscuity appears to be an adaptation to match a broad specificity of hydroxycinnamate catabolic enzymes while responding to toxic thioester intermediates. Structures of apo-HcaR and in complex with a specific DNA hca operator when combined with binding studies of hydroxycinnamates show how aromatic ligands render HcaR unproductive in recognizing a specific DNA target. Furthermore, the current study contributes to a better understanding of the hca catabolic operon regulation mechanism by the transcription factor HcaR.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23) - National Institutes of Health (NIH)
OSTI Identifier:
1769432
Alternate Identifier(s):
OSTI ID: 1337156
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Published Article
Journal Name:
Journal of Biological Chemistry
Additional Journal Information:
Journal Name: Journal of Biological Chemistry Journal Volume: 291 Journal Issue: 25; Journal ID: ISSN 0021-9258
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; bacterial transcription; DNA-binding protein; ligand-binding protein; metabolic regulation; protein conformation; DNA binding; human gut bacteria; NUDIX family; arabinose utilization; ligand-induced conformationional change

Citation Formats

Kim, Youngchang, Joachimiak, Grazyna, Bigelow, Lance, Babnigg, Gyorgy, and Joachimiak, Andrzej. How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator. United States: N. p., 2016. Web. doi:10.1074/jbc.M115.712067.
Kim, Youngchang, Joachimiak, Grazyna, Bigelow, Lance, Babnigg, Gyorgy, & Joachimiak, Andrzej. How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator. United States. https://doi.org/10.1074/jbc.M115.712067
Kim, Youngchang, Joachimiak, Grazyna, Bigelow, Lance, Babnigg, Gyorgy, and Joachimiak, Andrzej. Wed . "How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator". United States. https://doi.org/10.1074/jbc.M115.712067.
@article{osti_1769432,
title = {How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator},
author = {Kim, Youngchang and Joachimiak, Grazyna and Bigelow, Lance and Babnigg, Gyorgy and Joachimiak, Andrzej},
abstractNote = {Bacterial catabolism of aromatic compounds from various sources including phenylpropanoids and flavonoids that are abundant in soil plays an important role in the recycling of carbon in the ecosystem. We have determined the crystal structures of apo-HcaR from Acinetobacter sp. ADP1, a MarR/SlyA transcription factor, in complexes with hydroxycinnamates and a specific DNA operator. The protein regulates the expression of the hca catabolic operon in Acinetobacter and related bacterial strains, allowing utilization of hydroxycinnamates as sole sources of carbon. HcaR binds multiple ligands, and as a result the transcription of genes encoding several catabolic enzymes is increased. The 1.9-2.4 Å resolution structures presented here explain how HcaR recognizes four ligands (ferulate, 3,4-dihydroxybenzoate, p-coumarate, and vanillin) using the same binding site. The ligand promiscuity appears to be an adaptation to match a broad specificity of hydroxycinnamate catabolic enzymes while responding to toxic thioester intermediates. Structures of apo-HcaR and in complex with a specific DNA hca operator when combined with binding studies of hydroxycinnamates show how aromatic ligands render HcaR unproductive in recognizing a specific DNA target. Furthermore, the current study contributes to a better understanding of the hca catabolic operon regulation mechanism by the transcription factor HcaR.},
doi = {10.1074/jbc.M115.712067},
journal = {Journal of Biological Chemistry},
number = 25,
volume = 291,
place = {United States},
year = {Wed Jun 01 00:00:00 EDT 2016},
month = {Wed Jun 01 00:00:00 EDT 2016}
}

Journal Article:
Free Publicly Available Full Text
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https://doi.org/10.1074/jbc.M115.712067

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Cited by: 15 works
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