How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator

Kim, Youngchang; Joachimiak, Grazyna; Bigelow, Lance; Babnigg, Gyorgy; Joachimiak, Andrzej

doi:10.1074/jbc.M115.712067

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

Journal Article · Wed Jun 01 00:00:00 EDT 2016 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.M115.712067· OSTI ID:1769432

Kim, Youngchang; Joachimiak, Grazyna; Bigelow, Lance; Babnigg, Gyorgy; Joachimiak, Andrzej

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.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23) - National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1769432

Alternate ID(s):: OSTI ID: 1337156

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Vol. 291 Journal Issue: 25; ISSN 0021-9258

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 15 works

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59 BASIC BIOLOGICAL SCIENCES
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Title: How Aromatic Compounds Block DNA Binding of HcaR Catabolite Regulator

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