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| {{STRUCTURE_3b6a| PDB=3b6a | SCENE= }} | | {{STRUCTURE_3b6a| PDB=3b6a | SCENE= }} |
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| '''Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with actinorhodin'''
| | ===Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with actinorhodin=== |
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| ==Overview==
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| Actinorhodin, an antibiotic produced by Streptomyces coelicolor, is exported from the cell by the ActA efflux pump. actA is divergently transcribed from actR, which encodes a TetR-like transcriptional repressor. We showed previously that ActR represses transcription by binding to an operator from the actA/actR intergenic region. Importantly, actinorhodin itself or various actinorhodin biosynthetic intermediates can cause ActR to dissociate from its operator, leading to derepression. This suggests that ActR may mediate timely self-resistance to an endogenously produced antibiotic by responding to one of its biosynthetic precursors. Here, we report the structural basis for this precursor-mediated derepression with crystal structures of homodimeric ActR by itself and in complex with either actinorhodin or the actinorhodin biosynthetic intermediate (S)-DNPA [4-dihydro-9-hydroxy-1-methyl-10-oxo-3-H-naphtho-[2,3-c]-pyran-3-(S)-aceti c acid]. The ligand-binding tunnel in each ActR monomer has a striking hydrophilic/hydrophobic/hydrophilic arrangement of surface residues that accommodate either one hexacyclic actinorhodin molecule or two back-to-back tricyclic (S)-DNPA molecules. Moreover, our work also reveals the strongest structural evidence to date that TetR-mediated antibiotic resistance may have been acquired from an antibiotic-producer organism.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18207163}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18207163 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18207163}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Transcription regulation]] | | [[Category: Transcription regulation]] |
| [[Category: Transcriptional repressor]] | | [[Category: Transcriptional repressor]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:25:58 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:46:32 2008'' |
