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PDBsum entry 2r6f
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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 structure of bacillus stearothermophilus uvra provides insight into ATP-Modulated dimerization, Uvrb interaction, And DNA binding.
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Authors
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D.Pakotiprapha,
Y.Inuzuka,
B.R.Bowman,
G.F.Moolenaar,
N.Goosen,
D.Jeruzalmi,
G.L.Verdine.
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Ref.
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Mol Cell, 2008,
29,
122-133.
[DOI no: ]
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PubMed id
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Abstract
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The nucleotide excision repair pathway corrects many structurally unrelated DNA
lesions. Damage recognition in bacteria is performed by UvrA, a member of the
ABC ATPase superfamily whose functional form is a dimer with four
nucleotide-binding domains (NBDs), two per protomer. In the 3.2 A structure of
UvrA from Bacillus stearothermophilus, we observe that the nucleotide-binding
sites are formed in an intramolecular fashion and are not at the dimer interface
as is typically found in other ABC ATPases. UvrA also harbors two unique
domains; we show that one of these is required for interaction with UvrB, its
partner in lesion recognition. In addition, UvrA contains three zinc modules,
the number and ligand sphere of which differ from previously published models.
Structural analysis, biochemical experiments, surface electrostatics, and
sequence conservation form the basis for models of ATP-modulated dimerization,
UvrA-UvrB interaction, and DNA binding during the search for lesions.
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Figure 2.
Figure 2. Structural Comparison of the NBDs of BstUvrA and
Other ABC ATPases
The conserved ATPase motifs are colored
as follows: Walker A/P loop, green; Walker B and D loop, orange;
ABC signature motif, blue; Q loop, magenta; and H loop/switch,
cyan.
(A) Arrangement of the NBDs in E. coli MalK,
Pyrococcus furiosus RLI, and BstUvrA. Key residues important for
nucleotide binding and interactions across the dimer interface
are shown. The transmembrane portion of MalK is depicted in
transparent yellow.
(B) NBDs of UvrA were superimposed with
the NBDs of the maltose transporter MalK (ADP-bound, PDB code
2AWO; ATP-bound, PDB code 1Q12), and Rad50 (ATP-bound, PDB code
1F2U) using their respective ATP-binding domains. All the motifs
are from the same NBD except for the ABC signature motif and the
D loop, which are part of the opposing NBD. The bound ADP is
from the proximal site of UvrA protomer A and is represented as
ball and stick.
(C) Histogram showing the distance between
the C[α] atoms of the conserved Lys residue in the Walker A
motif and Ser residue in the ABC signature motif in the
structures of ABC ATPases solved in the dimeric state (PDB codes
2R6F, 2AWO, 1Q1B, 1Q1E, 2AWN, 1YQT, 1L7V, 2ONK, 1Q12, 1F2U,
1XEF, 1XEX).
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Figure 4.
Figure 4. BstUvrA Dimer Interface
C[α] trace of
protomers A and B are shown in pale green and pale blue,
respectively, with the Zn atoms in gray. The regions involved in
polar contacts across the dimer interface are shown using ribbon
diagram (green and orange, protomer A; blue and magenta,
protomer B). Hydrogen bonds are depicted as dashed lines and the
bound ADP molecules as space-filling models. Illustrations in
(A) –(C) are shown in the same orientation as in Figure 1B.
(A) UvrA dimer.
(B) Interactions between the Q loop-I
and the loop following α helix 1, which contains the Walker A-I
motif at its N terminus.
(C) Interactions between the loop
preceding Walker B-I and residues of the ATP-binding domain I of
the opposing monomer.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Mol Cell
(2008,
29,
122-133)
copyright 2008.
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