3B6A

Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with actinorhodin

3B6A の概要

• エントリーDOI: 10.2210/pdb3b6a/pdb
• 関連するPDBエントリー: 2OPT 3B6C
• 分子名称: ActR protein, 2,2'-[(1R,1'R,3S,3'S)-6,6',9,9'-tetrahydroxy-1,1'-dimethyl-5,5',10,10'-tetraoxo-3,3',4,4',5,5',10,10'-octahydro-1H,1'H-8,8'-bibenzo[g]isochromene-3,3'-diyl]diacetic acid (2 entities in total)
• 機能のキーワード: transcriptional repressor, dna-binding protein, tetr family, actinorhodin, ligand, transcription regulation, transcription
• 由来する生物種: Streptomyces coelicolor
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 206680.76

構造登録者

Willems, A.R.,Junop, M.S. (登録日: 2007-10-28, 公開日: 2008-02-05, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.05 Å)