1bjy
From Proteopedia
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'''TETRACYCLINE CHELATED MG2+-ION INITIATES HELIX UNWINDING FOR TET REPRESSOR INDUCTION''' | '''TETRACYCLINE CHELATED MG2+-ION INITIATES HELIX UNWINDING FOR TET REPRESSOR INDUCTION''' | ||
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[[Category: Orth, P.]] | [[Category: Orth, P.]] | ||
[[Category: Saenger, W.]] | [[Category: Saenger, W.]] | ||
- | [[Category: | + | [[Category: Dna-binding protein]] |
- | [[Category: | + | [[Category: Hth-motif]] |
- | [[Category: | + | [[Category: Transcription regulation]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:36:45 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 08:36, 2 May 2008
TETRACYCLINE CHELATED MG2+-ION INITIATES HELIX UNWINDING FOR TET REPRESSOR INDUCTION
Overview
The homodimeric tetracycline repressor (TetR) regulates resistance to the antibiotic tetracycline at the transcriptional level. TetR binds in the absence of Tc to palindromic operator sequences utilizing two helix-turn-helix (HTH) motifs. If the tetracycline-Mg2+ complex [MgTc]+ enters two identical binding tunnels buried within the TetR homodimer, a conformational change takes place, and the induced [TetR/[MgTc]+]2 complex releases operator DNA. To demonstrate the contribution of Mg2+ to [MgTc]+ binding and TetR induction, the Mg2+ concentration in the induced TetR homodimer was progressively reduced by addition of EDTA, resulting in two X-ray crystal structures of Mg2+-free and half-occupied TetR(D). Tc remains bound to the [MgTc]+-binding sites, despite the complete or partial absence of Mg2+. Together with inducer-free TetR(D), the structures were refined to between 2.2 and 2.7 A resolution and compared with fully induced TetR(D) in complex with two [MgTc]+. Each inducer binding tunnel has three constituent parts, one hydrophobic and two hydrophilic ones. One of the hydrophilic contact areas binds Tc by hydrogen bonding; the hydrophobic region correctly positions Tc and partially closes the entrance to the binding tunnel; the second hydrophilic region coordinates Mg2+, transduces the induction signal, and completes the process of closing the tunnel entrance. Tc confers binding specificity to TetR while Mg2+ is primarily responsible for induction: After binding to the imidazole Nepsilon of His100, Mg2+ is octahedrally coordinated to the 1,3-ketoenolate group of Tc and to three water molecules. One of these waters forms a hydrogen bond to the hydroxyl group Ogamma of Thr103. The induced 2.5 A movement of Thr103 results in the partial unwinding of helix alpha6, associated with a lateral shift of helices alpha4 and alpha9. They simultaneously close the tunnel entrance and cause the DNA-binding domains to adopt a nonbinding conformation, leading to release of operator DNA and expression of the genes responsible for resistance.
About this Structure
1BJY is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
Tetracycline-chelated Mg2+ ion initiates helix unwinding in Tet repressor induction., Orth P, Saenger W, Hinrichs W, Biochemistry. 1999 Jan 5;38(1):191-8. PMID:9890898 Page seeded by OCA on Fri May 2 11:36:45 2008