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PDBsum entry 1fzp
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Transcription/DNA
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PDB id
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1fzp
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Contents |
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* Residue conservation analysis
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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 sara, A pleiotropic regulator of virulence genes in s. Aureus.
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Authors
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M.A.Schumacher,
B.K.Hurlburt,
R.G.Brennan.
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Ref.
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Nature, 2001,
409,
215-219.
[DOI no: ]
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PubMed id
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Abstract
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Staphylococcus aureus is a major human pathogen, the potency of which can be
attributed to the regulated expression of an impressive array of virulence
determinants. A key pleiotropic transcriptional regulator of these virulence
factors is SarA, which is encoded by the sar (staphylococcal accessory
regulator) locus. SarA was characterized initially as an activator of a second
virulence regulatory locus, agr, through its interaction with a series of heptad
repeats (AGTTAAG) within the agr promoter. Subsequent DNA-binding studies have
revealed that SarA binds readily to multiple AT-rich sequences of variable
lengths. Here we describe the crystal structure of SarA and a SarA-DNA complex
at resolutions of 2.50 A and 2.95 A, respectively. SarA has a fold consisting of
a four-helix core region and 'inducible regions' comprising a beta-hairpin and a
carboxy-terminal loop. On binding DNA, the inducible regions undergo marked
conformational changes, becoming part of extended and distorted alpha-helices,
which encase the DNA. SarA recognizes an AT-rich site in which the DNA is highly
overwound and adopts a D-DNA-like conformation by indirect readout. These
structures thus provide insight into SarA-mediated transcription regulation.
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Figure 1.
Figure 1: The SarA dimer and SarA -DNA complex. a, Views of
SarA looking directly into the DNA-binding pocket or from the
'back' side. The secondary structures,  -hairpin
and C-terminal loop of one monomer are labelled. Each monomer is
red or green. b, The SarA -DNA complex in the identical
orientation of the corresponding apo SarA directly above. The
DNA duplex is shown as CPK atoms, with carbon, nitrogen, oxygen
and phosphates coloured white, blue, red and yellow,
respectively. The  4B
gripper helix of one monomer is also labelled. The narrow and
deep minor groove and major groove are seen on the left and
right respectively.
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Figure 2.
Figure 2: SarA inducible regions. a, Superimposed SarA
monomers of the DNA-bound and apo protein. The core region is
blue and the inducible regions are yellow and magenta for the
apo and DNA bound proteins, respectively. The hinge is labelled.
b , Conformational changes induced by DNA binding. The apo form
is shown on top (inducible regions in yellow) and the DNA-bound
form below (inducible regions in magenta). The DNA duplex and
Cys 9 side chains, which line the DNA binding channel, are shown
as CPK atoms, with carbon, nitrogen, oxygen and
phosphate/sulphur coloured white, blue, red and yellow,
respectively.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nature
(2001,
409,
215-219)
copyright 2001.
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