2opt

From Proteopedia

Revision as of 11:25, 5 March 2008

Crystal Structure of Apo ActR from Streptomyces coelicolor.

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

2OPT is a Single protein structure of sequence from Streptomyces coelicolor. 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 Mar 7;376(5):1377-87. Epub 2008 Jan 4. PMID:18207163

Page seeded by OCA on Wed Mar 5 13:25:31 2008