3B6C

Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with (S)-DNPA

Summary for 3B6C

• Entry DOI: 10.2210/pdb3b6c/pdb
• Related: 2OPT 3B6A
• Descriptor: ActII protein, [(3S)-9-hydroxy-1-methyl-10-oxo-4,10-dihydro-3H-benzo[g]isochromen-3-yl]acetic acid (3 entities in total)
• Functional Keywords: transcriptional repressor, dna-binding protein, tetr family, actinorhodin, (s)-dnpa, ligand, transcription regulation, transcription
• Biological source: Streptomyces coelicolor
• Total number of polymer chains: 2
• Total formula weight: 51259.95

Authors

Willems, A.R.,Junop, M.S. (deposition date: 2007-10-28, release date: 2008-02-05, Last modification date: 2023-08-30)

Primary citation

Willems, A.R.,Tahlan, K.,Taguchi, T.,Zhang, K.,Lee, Z.Z.,Ichinose, K.,Junop, M.S.,Nodwell, J.R.
Crystal structures of the Streptomyces coelicolor TetR-like protein ActR alone and in complex with actinorhodin or the actinorhodin biosynthetic precursor (S)-DNPA.
J.Mol.Biol., 376:1377-1387, 2008

PubMed Abstract: 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)-acetic 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.

PubMed: 18207163
DOI: 10.1016/j.jmb.2007.12.061

Experimental method

X-RAY DIFFRACTION (2.3 Å)