2Y31

Simocyclinone C4 bound form of TetR-like repressor SimR

2Y31 の概要

• エントリーDOI: 10.2210/pdb2y31/pdb
• 関連するPDBエントリー: 2Y2Z 2Y30
• 分子名称: PUTATIVE REPRESSOR SIMREG2, SIMOCYCLINONE C4, PENTAETHYLENE GLYCOL, ... (7 entities in total)
• 機能のキーワード: transcription, tetr-family
• 由来する生物種: STREPTOMYCES ANTIBIOTICUS
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62682.01

構造登録者

Le, T.B.K.,Stevenson, C.E.M.,Fiedler, H.-P.,Maxwell, A.,Lawson, D.M.,Buttner, M.J. (登録日: 2010-12-17, 公開日: 2011-03-09, 最終更新日: 2023-12-20)

主引用文献

Le, T.B.K.,Stevenson, C.E.M.,Fiedler, H.-P.,Maxwell, A.,Lawson, D.M.,Buttner, M.J.
Structures of the Tetr-Like Simocyclinone Efflux Pump Repressor, Simr, and the Mechanism of Ligand-Mediated Derepression.
J.Mol.Biol., 408:40-, 2011

PubMed Abstract: Simocyclinone D8 (SD8), a potent DNA gyrase inhibitor made by Streptomyces antibioticus, is exported from the producing organism by the SimX efflux pump. The expression of simX is under the control of SimR, a member of the TetR family of transcriptional regulators. SimR represses simX transcription by binding to operators in the intergenic region between simR and simX. Previously, we have shown that the mature antibiotic SD8 or its biosynthetic intermediate, simocyclinone C4, can dissociate SimR from its operators, leading to derepression of simX and export of SD8 from the cell. This provides a mechanism that couples the biosynthesis of the antibiotic to its export. Here, we report the crystal structures of SimR alone and in complex with either SD8 or simocyclinone C4. The ligand-binding pocket is unusual compared to those of other characterized TetR-family transcriptional regulators: the structures show an extensive ligand-binding pocket spanning both monomers in the functional dimeric unit, with the aminocoumarin moiety of SD8 buried in the protein core, while the angucyclic polyketide moiety is partially exposed to bulk solvent. Through comparisons of the structures, we postulate a derepression mechanism for SimR that invokes rigid-body motions of the subunits relative to one another, coupled with a putative locking mechanism to restrict further conformational change.

PubMed: 21354180
DOI: 10.1016/J.JMB.2011.02.035

実験手法

X-RAY DIFFRACTION (2.3 Å)