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PDBsum entry 2bfq
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Adp ribose-binding protein
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PDB id
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2bfq
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References listed in PDB file
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Key reference
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Title
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The macro domain is an ADP-Ribose binding module.
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Authors
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G.I.Karras,
G.Kustatscher,
H.R.Buhecha,
M.D.Allen,
C.Pugieux,
F.Sait,
M.Bycroft,
A.G.Ladurner.
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Ref.
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EMBO J, 2005,
24,
1911-1920.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
71%.
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Abstract
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The ADP-ribosylation of proteins is an important post-translational modification
that occurs in a variety of biological processes, including DNA repair,
transcription, chromatin biology and long-term memory formation. Yet no protein
modules are known that specifically recognize the ADP-ribose nucleotide. We
provide biochemical and structural evidence that macro domains are high-affinity
ADP-ribose binding modules. Our structural analysis reveals a conserved ligand
binding pocket among the macro domain fold. Consistently, distinct human macro
domains retain their ability to bind ADP-ribose. In addition, some macro domain
proteins also recognize poly-ADP-ribose as a ligand. Our data suggest an
important role for proteins containing macro domains in the biology of
ADP-ribose.
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Figure 4.
Figure 4 Structure of the complex formed between Af1521 and
ADP-ribose. (A) The ADP-ribose molecule binds the Af1521 macro
domain in an L-shaped cleft. The ADP-ribose ligand is shown as a
ball-and-stick model. (B) Structure of the complex between
Af1521 and ADP. The structure is highly similar to that of the
complex between Af1521 and ADP-ribose, but a number of
interactions that contribute to ADP-ribose specificity and
affinity cannot occur. The ADP ligand is shown as a
ball-and-stick model.
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Figure 5.
Figure 5 Specificity of the macro domain fold for ADP-ribose.
(A) Electron density for the ADP-ribose ligand in the pocket of
the Af1521 protein. The ADP-ribose ligand is shown as a
ball-and-stick model. (B) Stereo-diagram of the ADP-ribose
binding pocket. A number of critical interactions between the
ligand and the Af1521 macro domain are shown. Several of the
interactions involve hydrogen bonds between side chains (Asn 34,
Asp 20) and backbone amide bonds. Specific aromatic stacking
interactions occur between Tyr 176 and the adenine base. The
phosphates are stabilized by a number of interactions, including
the backbone amide of Val 43, Ser 141 and the favorable dipole
of helix 1. (C) Schematic representation for the binding of
ADP-ribose to the macro domain. The LigPlot (Wallace et al,
1995) diagram summarizes key noncovalent interactions between
the ADP-ribose ligand and the Af1521 macro domain. Legend: thick
blue lines, ADP-ribose ligand; thin red lines, macro domain
residues; circles or semicircles with radiating lines; atoms or
residues involved in hydrophobic contacts between protein and
ligand.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(2005,
24,
1911-1920)
copyright 2005.
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