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PDBsum entry 4zsb
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Transcription
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PDB id
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4zsb
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References listed in PDB file
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Key reference
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Title
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Crystal structures of the global regulator dasr from streptomyces coelicolor: implications for the allosteric regulation of gntr/hutc repressors.
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Authors
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S.B.Fillenberg,
M.D.Friess,
S.Körner,
R.A.Böckmann,
Y.A.Muller.
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Ref.
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Plos One, 2016,
11,
e0157691.
[DOI no: ]
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PubMed id
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Abstract
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Small molecule effectors regulate gene transcription in bacteria by altering the
DNA-binding affinities of specific repressor proteins. Although the GntR
proteins represent a large family of bacterial repressors, only little is known
about the allosteric mechanism that enables their function. DasR from
Streptomyces coelicolor belongs to the GntR/HutC subfamily and specifically
recognises operators termed DasR-responsive elements (dre-sites). Its
DNA-binding properties are modulated by phosphorylated sugars. Here, we present
several crystal structures of DasR, namely of dimeric full-length DasR in the
absence of any effector and of only the effector-binding domain (EBD) of DasR
without effector or in complex with glucosamine-6-phosphate (GlcN-6-P) and
N-acetylglucosamine-6-phosphate (GlcNAc-6-P). Together with molecular dynamics
(MD) simulations and a comparison with other GntR/HutC family members these data
allowed for a structural characterisation of the different functional states of
DasR. Allostery in DasR and possibly in many other GntR/HutC family members is
best described by a conformational selection model. In ligand-free DasR, an
increased flexibility in the EBDs enables the attached DNA-binding domains (DBD)
to sample a variety of different orientations and among these also a DNA-binding
competent conformation. Effector binding to the EBDs of DasR significantly
reorganises the atomic structure of the latter. However, rather than locking the
orientation of the DBDs, the effector-induced formation of β-strand β* in the
DBD-EBD-linker segment merely appears to take the DBDs 'on a shorter leash'
thereby impeding the 'downwards' positioning of the DBDs that is necessary for a
concerted binding of two DBDs of DasR to operator DNA.
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