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PDBsum entry 3ger
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References listed in PDB file
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Key reference
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Title
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Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs.
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Authors
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S.D.Gilbert,
F.E.Reyes,
A.L.Edwards,
R.T.Batey.
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Ref.
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Structure, 2009,
17,
857-868.
[DOI no: ]
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PubMed id
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Abstract
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Purine riboswitches discriminate between guanine and adenine by at least
10,000-fold based on the identity of a single pyrimidine (Y74) that forms a
Watson-Crick base pair with the ligand. To understand how this high degree of
specificity for closely related compounds is achieved through simple pairing, we
investigated their interaction with purine analogs with varying functional
groups at the 2- and 6-positions that have the potential to alter interactions
with Y74. Using a combination of crystallographic and calorimetric approaches,
we find that binding these purines is often facilitated by either small
structural changes in the RNA or tautomeric changes in the ligand. This work
also reveals that, along with base pairing, conformational restriction of Y74
significantly contributes to nucleobase selectivity. These results reveal that
compounds that exploit the inherent local flexibility within riboswitch binding
pockets can alter their ligand specificity.
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Figure 1.
Figure 1. Ligand Binding Site of the Purine Riboswitch and
Chemicals
(A) Details of hypoxanthine (top, PDB 1U8D) and
adenine (bottom, PDB 1Y26) bound to the guanine and adenine
riboswitches, respectively. The specificity pyrimidine (C74 or
U74, yellow) forms hydrogen bonds (red dashed lines) to the
Watson-Crick face of the ligand (pink), whereas U51, U47, and
U22 interact with the other faces of the purine nucleobase.
Residues are colored according to their strand position in the
junction region. Note that the hydrogen bonding pattern for
ligand recognition is identical.
(B) Chemical structures of
purine derivatives characterized in this study.
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Figure 5.
Figure 5. 6-Position Derivatives Complexed to an Adenine
Binding RNA
(A) Structure of 6ClG bound to GRA; double
arrow represents a potential halogen bond between the chloro
group and U74.
(B) Binding pocket of the 6OMeG:GRA complex;
arrow denotes a long hydrogen bond (3.5 Å) between
N1(6OMeG) and N3(U74).
(C) Superposition of structures of
the wild-type hypoxanthine:GR complex (red), 6ClG:GRA (blue),
and 6OMeG:GRA (green). Most atoms in each structure superimpose
well, except for a minor repulsion between the ligand and U74 in
the 6OMeG:GRA complex to accommodate the methyl group at the
Watson-Crick interface.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2009,
17,
857-868)
copyright 2009.
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Headers
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