PDBsum entry 4d7n

Transcription

PDB id: 4d7n

Contents

Protein chain

197 a.a.

Ligands

TDC

Metals

_CL ×4

__K ×2

Waters ×156

PDB id:

4d7n

Name:

Transcription

Title:

Tetr(d) in complex with anhydrotetracycline and potassium

Structure:

Tetracycline repressor, class d. Chain: a. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 83333.

Resolution:

1.76Å R-factor: 0.191 R-free: 0.225

Authors:

S.Werten,D.Dalm,G.J.Palm,W.Hinrichs

Key ref:

S.Werten et al. (2014). Tetracycline repressor allostery does not depend on divalent metal recognition. Biochemistry, 53, 7990-7998. PubMed id: 25432019 DOI: 10.1021/bi5012805

Date:

25-Nov-14 Release date: 10-Dec-14

Supersedes:

2xpt

Protein chain

A0A017KEE3  () -

DOI no: 10.1021/bi5012805

Biochemistry 53:7990-7998 (2014)

PubMed id: 25432019

Tetracycline repressor allostery does not depend on divalent metal recognition.

S.Werten, D.Dalm, G.J.Palm, C.C.Grimm, W.Hinrichs.

ABSTRACT

Genes that render bacteria resistant to tetracycline-derived antibiotics are tightly regulated by repressors of the TetR family. In their physiologically relevant, magnesium-complexed form, tetracyclines induce allosteric rearrangements in the TetR homodimer, leading to its release from the promoter and derepression of transcription. According to earlier crystallographic work, recognition of the tetracycline-associated magnesium ion by TetR is crucial and triggers the allosteric cascade. Nevertheless, the derivative 5a,6-anhydrotetracycline, which shows an increased affinity for TetR, causes promoter release even in the absence of magnesium. To resolve this paradox, it has been proposed that metal-free 5a,6-anhydrotetracycline acts via an exceptional, conformationally different induction mode that circumvents the normal magnesium requirement. We have tested this hypothesis by determining crystal structures of TetR-5a,6-anhydrotetracycline complexes in the presence of magnesium, ethylenediaminetetraacetic acid, or high concentrations of potassium. Analysis of these three structures reveals that, irrespective of the metal, the effects of 5a,6-anhydrotetracycline binding are indistinguishable from those of canonical induction by other tetracyclines. Together with a close scrutiny of the earlier evidence of a metal-triggered mechanism, these results demonstrate that magnesium recognition per se is not a prerequisite for tetracycline repressor allostery.