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PDBsum entry 1xcb
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DNA binding protein
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PDB id
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1xcb
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Contents |
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(+ 0 more)
205 a.a.
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192 a.a.
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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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X-Ray structure of a rex-Family repressor/nadh complex insights into the mechanism of redox sensing.
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Authors
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E.A.Sickmier,
D.Brekasis,
S.Paranawithana,
J.B.Bonanno,
M.S.Paget,
S.K.Burley,
C.L.Kielkopf.
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Ref.
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Structure, 2005,
13,
43-54.
[DOI no: ]
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PubMed id
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Abstract
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The redox-sensing repressor Rex regulates transcription of respiratory genes in
response to the intra cellular NADH/NAD(+) redox poise. As a step toward
elucidating the molecular mechanism of NADH/NAD(+) sensing, the X-ray structure
of Thermus aquaticus Rex (T-Rex) bound to effector NADH has been determined at
2.9 A resolution. The fold of the C-terminal domain of T-Rex is characteristic
of NAD(H)-dependent enzymes, whereas the N-terminal domain is similar to a
winged helix DNA binding motif. T-Rex dimerization is primarily mediated by
"domain-swapped" alpha helices. Each NADH molecule binds to the
C-terminal domain near the dimer interface. In contrast to NAD(H)-dependent
enzymes, the nicotinamide is deeply buried within a hydrophobic pocket that
appears to preclude substrate entry. We show that T-Rex binds to the Rex
operator, and NADH but not NAD(+) inhibits T-Rex/DNA binding activity. A
mechanism for redox sensing by Rex family members is proposed by analogy with
domain closure of NAD(H)-dependent enzymes.
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Figure 6.
Figure 6. The T-Rex NAD(H) Binding Sites and Comparison
with NAD(H)-Dependent Dehydrogenase
(A) T-Rex interactions
with the NADH effector molecule, in the conformation with Phe189
inserted between the nicotinamide rings. Average distances
between interacting atoms of the three subunits exhibiting this
conformation are indicated.
(B) T-Rex interactions with the
NADH' molecule bound to the opposite subunit, in the
conformation with Phe189 folded back and buried within the
hydrophobic core.
(C) LADH interactions with bound NADH,
zinc ion (ZN), and DMSO substrate.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2005,
13,
43-54)
copyright 2005.
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