3b6c: Difference between revisions
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''''''<br /> | '''Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with (S)-DNPA'''<br /> | ||
==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== | ==About this Structure== | ||
3B6C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor] with <scene name='pdbligand=SDN:'>SDN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Sdn+Binding+Site+For+Residue+A+301'>AC1</scene>, <scene name='pdbsite=AC2:Sdn+Binding+Site+For+Residue+A+302'>AC2</scene> and <scene name='pdbsite=AC3:Sdn+Binding+Site+For+Residue+B+303'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B6C OCA]. | |||
[[Category: | |||
==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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18207163 18207163] | |||
[[Category: Single protein]] | |||
[[Category: Streptomyces coelicolor]] | |||
[[Category: Junop, M.S.]] | |||
[[Category: Willems, A.R.]] | |||
[[Category: SDN]] | |||
[[Category: (s)-dnpa]] | |||
[[Category: actinorhodin]] | |||
[[Category: dna-binding protein]] | |||
[[Category: ligand]] | |||
[[Category: tetr family]] | |||
[[Category: transcription regulation]] | |||
[[Category: transcriptional repressor]] | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 6 17:25:37 2008'' | ||
Revision as of 15:25, 6 February 2008
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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 SDN as ligand. Known structural/functional Sites: AC1, AC2 and AC3. 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
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