3b6c
From Proteopedia
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Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with (S)-DNPA
Overview
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.
About this Structure
3B6C is a Single protein structure of sequence from Streptomyces coelicolor with as ligand. Known structural/functional Sites: , and . Full crystallographic information is available from OCA.
Reference
Crystal Structures of the Streptomyces coelicolor TetR-Like Protein ActR Alone and in Complex with Actinorhodin or the Actinorhodin Biosynthetic Precursor (S)-DNPA., Willems AR, Tahlan K, Taguchi T, Zhang K, Lee ZZ, Ichinose K, Junop MS, Nodwell JR, J Mol Biol. 2008 Jan 4;. PMID:18207163
Page seeded by OCA on Wed Feb 6 17:25:37 2008
