PDBsum entry 3b6c

Transcription

PDB id: 3b6c

Contents

Protein chains

202 a.a. *

Ligands

SDN ×3

Waters ×146

* Residue conservation analysis

PDB id:

3b6c

Name:

Transcription

Title:

Crystal structure of the streptomyces coelicolor tetr family protein actr in complex with (s)-dnpa

Structure:

Actii protein. Chain: a, b. Synonym: putative transcriptional regulatory protein. Engineered: yes

Source:

Streptomyces coelicolor. Organism_taxid: 1902. Strain: m145. Gene: actii. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

2.30Å R-factor: 0.246 R-free: 0.287

Authors:

A.R.Willems,M.S.Junop

Key ref:

A.R.Willems et al. (2008). 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. PubMed id: 18207163 DOI: 10.1016/j.jmb.2007.12.061

Date:

28-Oct-07 Release date: 05-Feb-08

Protein chains

Q53901  (Q53901_STRCH) -  ActII protein from Streptomyces coelicolor

Seq: 259 a.a.

Struc: 202 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2007.12.061

J Mol Biol 376:1377-1387 (2008)

PubMed id: 18207163

Crystal structures of the Streptomyces coelicolor TetR-like protein ActR alone and in complex with actinorhodin or the actinorhodin biosynthetic precursor (S)-DNPA.

A.R.Willems, K.Tahlan, T.Taguchi, K.Zhang, Z.Z.Lee, K.Ichinose, M.S.Junop, J.R.Nodwell.

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.

Selected figure(s)

Figure 1.
Fig. 1. Actinorhodin biosynthesis and export. An initial polyketide is transformed via multiple enzyme-catalyzed steps into (S)-DNPA and, eventually, actinorhodin, which is exported from the cell. The proposed mechanism of export regulation by actinorhodin and (S)-DNPA is supported by recent studies that show that ActR can be derepressed by these compounds.^21 Numbering of selected carbon atoms based on biosynthetic origin is indicated. The broken line within actinorhodin indicates its internal bilateral symmetry.

Figure 5.
Fig. 5. The hydrogen-bonding network near the proximal ligand-binding site. Side chains and one backbone carbonyl group that form a hydrogen-bonding network in the ActR/(S)-DNPA structure are shown. The molecular protein surface of the proximal end of the ligand-binding tunnel of chain A is shown, as is the position of the proximal (S)-DNPA molecule. Note the proximity of the ligand carboxymethyl group and R225.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 376, 1377-1387) copyright 2008.

Figures were selected by an automated process.