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PDBsum entry 4ake
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Phosphotransferase
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PDB id
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4ake
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Adenylate kinase motions during catalysis: an energetic counterweight balancing substrate binding.
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Authors
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C.W.Müller,
G.J.Schlauderer,
J.Reinstein,
G.E.Schulz.
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Ref.
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Structure, 1996,
4,
147-156.
[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
perfect match.
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Abstract
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BACKGROUND: Adenylate kinases undergo large conformational changes during their
catalytic cycle. Because these changes have been studied by comparison of
structures from different species, which share approximately one-third of their
residues, only rough descriptions have been possible to date. RESULTS: We have
solved the structure of unligated adenylate kinase from Escherichia coli at 2.2
degree resolution and compared it with the high-resolution structure of the same
enzyme ligated with an inhibitor mimicking both substrates, ATP and AMP. This
comparison shows that, upon substrate binding, the enzyme increases its chain
mobility in a region remote from the active center. As this region 'solidifies'
again on substrate release, we propose that it serves as a 'counterweight'
balancing the substrate binding energy. CONCLUSION: The comparison of two very
different conformations of the same polypeptide chain revealed kinematic details
of the catalytic cycle. Moreover, it indicated that there exists an energetic
counterweight compensating the substrate binding energy required for
specificity. This counterweight prevents the enzyme from dropping into a
rate-reducing energy well along the reaction coordinate.
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Figure 3.
Figure 3. Stereo diagram illustrating the molecular packing in
the a–c plane of the P1 crystals (c horizontal). The slightly
asymmetric contacts between the LID domains of molecule I
(left) and molecule II (right) are visible. Figure 3. Stereo
diagram illustrating the molecular packing in the a–c plane of
the P1 crystals (c horizontal). The slightly asymmetric contacts
between the LID domains of molecule I (left) and molecule II
(right) are visible.
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Figure 8.
Figure 8. Kinematics at hinge H6 in the movement of domain LID
from an ‘open’ to the ‘closed’ state as derived from a
molecular dynamics simulation using X-PLOR [19]. The average
(φ, ψ) pathways of the ‘trigger’ residues are plotted with
dots at 0.5 ps intervals: S, start in the apo-AK[eco]
structure; E, end of simulated pathway; T, target value in the
AK[eco]:Ap[5]A structure. The averages are from 10 simulations
all of which run along similar pathways. The allowed regions
[18] of the (φ, ψ) plot are indicated by dotted lines.
Figure 8. Kinematics at hinge H6 in the movement of domain LID
from an ‘open’ to the ‘closed’ state as derived from a
molecular dynamics simulation using X-PLOR [[3]19]. The average
(φ, ψ) pathways of the ‘trigger’ residues are plotted with
dots at 0.5 ps intervals: S, start in the apo-AK[eco] structure;
E, end of simulated pathway; T, target value in the
AK[eco]:Ap[5]A structure. The averages are from 10 simulations
all of which run along similar pathways. The allowed regions
[[4]18] of the (φ, ψ) plot are indicated by dotted lines.
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The above figures are
reprinted
by permission from Cell Press:
Structure
(1996,
4,
147-156)
copyright 1996.
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Secondary reference #1
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Title
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Movie of the structural changes during a catalytic cycle of nucleoside monophosphate kinases.
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Authors
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C.Vonrhein,
G.J.Schlauderer,
G.E.Schulz.
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Ref.
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Structure, 1995,
3,
483-490.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. Ribbon representation of all established
structures used in the movie, including the ligands, which are
shown as ball and stick models. 1, AK[eco]:Ap[5]A; 2, AK[eco];
3, AK1; 4, AK2; 5, AK3:AMP; 6, AK3:AMP; 7, AK[yst]:Ap[5]A; 8,
AK[yst]:AMPPCF[2]P; 9, UK[yst]:ADP:ADP. For details see Table 1.
Figure 1. Ribbon representation of all established
structures used in the movie, including the ligands, which are
shown as ball and stick models. 1, AK[eco]:Ap[5]A; 2, AK[eco];
3, AK1; 4, AK2; 5, AK3:AMP; 6, AK3:AMP; 7, AK[yst]:Ap[5]A; 8,
AK[yst]:AMPPCF[2]P; 9, UK[yst]:ADP:ADP. For details see [3]Table
1.
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Figure 4.
Figure 4. Picture series 1 to 40 for the LID motion,
representing an equally spaced selection from the 90 pictures of
the movie. The observed structures, A to G, are indicated. The
pictures can be cut out and stapled at the left-hand side to
produce a flicker book, as described in the legend for Figure 3.
Figure 4. Picture series 1 to 40 for the LID motion,
representing an equally spaced selection from the 90 pictures of
the movie. The observed structures, A to G, are indicated. The
pictures can be cut out and stapled at the left-hand side to
produce a flicker book, as described in the legend for [3]Figure
3.
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The above figures are
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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Structure of the complex between adenylate kinase from escherichia coli and the inhibitor ap5a refined at 1.9 a resolution. A model for a catalytic transition state.
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Authors
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C.W.Müller,
G.E.Schulz.
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Ref.
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J Mol Biol, 1992,
224,
159-177.
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PubMed id
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