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PDBsum entry 1tae
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References listed in PDB file
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Key reference
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Title
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Structural rearrangement accompanying NAD+ synthesis within a bacterial DNA ligase crystal.
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Authors
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K.S.Gajiwala,
C.Pinko.
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Ref.
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Structure, 2004,
12,
1449-1459.
[DOI no: ]
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PubMed id
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Abstract
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DNA ligase is an enzyme important for DNA repair and replication. Eukaryotic
genomes encode ligases requiring ATP as the cofactor; bacterial genomes encode
NAD(+)-dependent ligase. This difference in substrate specificities and the
essentiality of NAD(+)-dependent ligase for bacterial survival make
NAD(+)-dependent ligase a good target for designing highly specific
anti-infectives. Any such structure-guided effort would require the knowledge of
the precise mechanism of NAD+ recognition by the enzyme. We report the
principles of NAD+ recognition by presenting the synthesis of NAD+ from
nicotinamide mononucleotide (NMN) and AMP, catalyzed by Enterococcus faecalis
ligase within the crystal lattice. Unprecedented conformational change, required
to reorient the two subdomains of the protein for the condensation to occur and
to recognize NAD+, is captured in two structures obtained using the same protein
crystal. Structural data and sequence analysis presented here confirms and
extends prior functional studies of the ligase adenylation reaction.
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Figure 5.
Figure 5. NAD^+ Recognition by Ef LigaseSome of the
interactions between polar atoms that are within 3.2 Å are shown
with dashes.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
1449-1459)
copyright 2004.
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Secondary reference #1
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Title
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Structure of the adenylation domain of an NAD+-Dependent DNA ligase.
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Authors
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M.R.Singleton,
K.Håkansson,
D.J.Timson,
D.B.Wigley.
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Ref.
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Structure, 1999,
7,
35-42.
[DOI no: ]
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PubMed id
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Figure 5.
Figure 5. Molecular surface of the adenylation domain
overlaid with the model for NAD^+ binding. This figure was
prepared using GRASP [11].
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The above figure is
reproduced from the cited reference
with permission from Cell Press
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Secondary reference #2
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Title
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Crystal structure of NAD(+)-Dependent DNA ligase: modular architecture and functional implications.
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Authors
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J.Y.Lee,
C.Chang,
H.K.Song,
J.Moon,
J.K.Yang,
H.K.Kim,
S.T.Kwon,
S.W.Suh.
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Ref.
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EMBO J, 2000,
19,
1119-1129.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2 Stereo C[  ]superposition
of Tfi DNA ligase. (A) One of the two crystallographically
independent ligase molecules in the native structure takes a
more closed conformation (gray) than the other (black), and its
BRCT domain is visible in the electron density map.
Superposition is made for domain 1. (B) Subdomain 1a of Bst
ligase (gray) takes a very different orientation from that of
Tfi ligase (black). Superposition is made for subdomain 1b.
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Figure 5.
Figure 5 Schematic model proposed for the Tfi ligase active
site. Residues that are likely to participate in binding metal
ions and the 5'-phosphate end of the nick are indicated.
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The above figures are
reproduced from the cited reference
which is an Open Access publication published by Macmillan Publishers Ltd
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