2OPT
Crystal Structure of Apo ActR from Streptomyces coelicolor.
Summary for 2OPT
| Entry DOI | 10.2210/pdb2opt/pdb |
| Descriptor | ActII protein (2 entities in total) |
| Functional Keywords | helical protein, tetr family, apo-protein, transcriptional repressor, transcription |
| Biological source | Streptomyces coelicolor |
| Total number of polymer chains | 2 |
| Total formula weight | 50401.11 |
| Authors | Willems, A.R.,Junop, M.S. (deposition date: 2007-01-30, release date: 2008-02-05, Last modification date: 2023-12-27) |
| 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 Cited by 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: 18207163DOI: 10.1016/j.jmb.2007.12.061 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
Download full validation report
