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PDBsum entry 2pid
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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 human mitochondrial tyrosyl-Trna synthetase reveals common and idiosyncratic features.
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Authors
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L.Bonnefond,
M.Frugier,
E.Touzé,
B.Lorber,
C.Florentz,
R.Giegé,
C.Sauter,
J.Rudinger-Thirion.
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Ref.
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Structure, 2007,
15,
1505-1516.
[DOI no: ]
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PubMed id
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Abstract
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We report the structure of a strictly mitochondrial human synthetase, namely
tyrosyl-tRNA synthetase (mt-TyrRS), in complex with an adenylate analog at 2.2 A
resolution. The structure is that of an active enzyme deprived of the C-terminal
S4-like domain and resembles eubacterial TyrRSs with a canonical
tyrosine-binding pocket and adenylate-binding residues typical of class I
synthetases. Two bulges at the enzyme surface, not seen in eubacterial TyrRSs,
correspond to conserved sequences in mt-TyrRSs. The synthetase electrostatic
surface potential differs from that of other TyrRSs, including the human
cytoplasmic homolog and the mitochondrial one from Neurospora crassa. The
homodimeric human mt-TyrRS shows an asymmetry propagating from the dimer
interface toward the two catalytic sites and extremities of each subunit.
Mutagenesis of the catalytic domain reveals functional importance of Ser200 in
line with an involvement of A73 rather than N1-N72 in tyrosine identity.
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Figure 3.
Figure 3. Conformational Asymmetry in Homodimeric Human
mt-TyrRS-ΔS4
Superimposition of the two subunits of
mt-TyrRS-ΔS4 in complex with Tyr-AMS (backbones colored as in
Figure 1A, in heavy and light colors for monomer A and B,
respectively). The regions with largest asymmetries are circled.
Note that the two adenylate analogs (in blue) almost perfectly
superimpose.
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Figure 7.
Figure 7. Role of Clusters 1 and 2 in tRNA^Tyr Acceptor Arm
Recognition
(A) Superimposition of the cleft formed by the
two helical structures of clusters 1 and 2 (in which binds the
tyrosine acceptor arm of tRNA^Tyr) in the crystallographic
structures of human mt-TyrRS (in brown), B. stearothermophilus
TyrRS (in blue), and T. thermophilus TyrRS in complex with
tRNA^Tyr (in green). Notice the quasiperfect superimposition of
the two clusters in human mt-TyrRS and B. stearothermophilus
TyrRS and the important structural deviations in T. thermophilus
TyrRS. The bar at the bottom of the figure shows the position
where the cleft is largest (d = 9.9, 10.0, and 12.4 Å in
the TyrRSs from human mitochondria, B. stearothermophilus, and
T. thermophilus, respectively, indicating an enlargement of the
cleft in T. thermophilus of  vert,
similar 2.5 Å). The three amino acids that were
mutagenized are indicated.
(B) View of the clusters and
their proximity with the tRNA acceptor branch as seen in the
crystal structure of the T. thermophilus complex (Yaremchuk et
al., 2002).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2007,
15,
1505-1516)
copyright 2007.
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Secondary reference #1
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Title
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Tyrosyl-Trna synthetase: the first crystallization of a human mitochondrial aminoacyl-Trna synthetase
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Authors
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L.Bonnefond,
M.Frugier,
E.Touze,
B.Lorber,
C.Florentz,
R.Giege,
J.Rudinger-Thirion,
C.Sauter.
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Ref.
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acta crystallogr ,sect f, 2007,
63,
338.
[DOI no: ]
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PubMed id
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Figure 3.
Figure 3. Conformational Asymmetry in Homodimeric Human
mt-TyrRS-ΔS4
Superimposition of the two subunits of
mt-TyrRS-ΔS4 in complex with Tyr-AMS (backbones colored as in
Figure 1A, in heavy and light colors for monomer A and B,
respectively). The regions with largest asymmetries are circled.
Note that the two adenylate analogs (in blue) almost perfectly
superimpose.
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Figure 7.
Figure 7. Role of Clusters 1 and 2 in tRNA^Tyr Acceptor Arm
Recognition
(A) Superimposition of the cleft formed by the
two helical structures of clusters 1 and 2 (in which binds the
tyrosine acceptor arm of tRNA^Tyr) in the crystallographic
structures of human mt-TyrRS (in brown), B. stearothermophilus
TyrRS (in blue), and T. thermophilus TyrRS in complex with
tRNA^Tyr (in green). Notice the quasiperfect superimposition of
the two clusters in human mt-TyrRS and B. stearothermophilus
TyrRS and the important structural deviations in T. thermophilus
TyrRS. The bar at the bottom of the figure shows the position
where the cleft is largest (d = 9.9, 10.0, and 12.4 Å in
the TyrRSs from human mitochondria, B. stearothermophilus, and
T. thermophilus, respectively, indicating an enlargement of the
cleft in T. thermophilus of vert,
similar 2.5 Å). The three amino acids that were
mutagenized are indicated.
(B) View of the clusters and
their proximity with the tRNA acceptor branch as seen in the
crystal structure of the T. thermophilus complex (Yaremchuk et
al., 2002).
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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