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PDBsum entry 2aqz
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Hormone/growth factor
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PDB id
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2aqz
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References listed in PDB file
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Key reference
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Title
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Conversion of type i 4:6 to 3:5 beta-Turn types in human acidic fibroblast growth factor: effects upon structure, Stability, Folding, And mitogenic function.
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Authors
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J.Lee,
V.K.Dubey,
T.Somasundaram,
M.Blaber.
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Ref.
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Proteins, 2006,
62,
686-697.
[DOI no: ]
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PubMed id
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Abstract
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Human acidic fibroblast growth factor (FGF-1) is a member of the beta-trefoil
superfold, a protein architecture that exhibits a characteristic threefold axis
of structural symmetry. FGF-1 contains 11 beta-turns, the majority being type I
3:5; however, a type I 4:6 turn is also found at three symmetry-related
locations. The relative uniqueness of the type I 4:6 turn in the FGF-1 structure
suggests it may play a key role in the stability, folding, or function of the
protein. To test this hypothesis a series of deletion mutations were
constructed, the aim of which was to convert existing type I 4:6 turns at two
locations into type I 3:5 turns. The results show it is possible to successfully
substitute the type I 4:6 turn by a type I 3:5 turn with minimal impact upon
protein stability or folding. Thus, these different turn structures, even though
they differ in length, exhibit similar energetic properties. Additional sequence
swapping mutations within the introduced type I 3:5 turns suggests that the turn
sequence primarily affects stability but not turn structure (which appears
dictated primarily by the local environment). Although the results suggest that
a stable, foldable beta-trefoil protein may be designed utilizing a single turn
type (type I 3:5), a type I 4:6 turn at turn 1 of FGF-1 appears essential for
efficient mitogenic function.
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Figure 2.
Figure 2. (Upper panel) Relaxed stereodiagram of an overlay of
the turn 1 region in the wild-type FGF-1 structure (light gray)
with that of the  G19
mutant (dark gray). Also shown is a 2F[o] - F[c] difference
electron density map of the G19
mutant contoured at 1.5  .
Turn 1 has converted from type I 4:6 in the wild-type structure
to a type I 3:5 in the G19
mutant. (Middle panel) Relaxed stereodiagram of an overlay of
the turn 5 region in the wild-type FGF-1 structure (light gray)
with that of the E60
mutant (dark gray). Also shown is a 2F[o] - F[c] difference
electron density map of the E60
mutant contoured at 1.5 .
Turn 5 has converted from type I 4:6 in the wild-type structure
to a type I 3:5 in the E60
mutant. (Lower panel) Relaxed stereodiagram of an overlay of the
turn 1 region in the G19
mutant structure (light gray) with that of the S17T/N18T/ G19
mutant (dark gray). Also shown is a 2F[o] - F[c] difference
electron density map of the S17T/N18T/ G19
mutant contoured at 1.5 .
The S17T/N18T mutations in the turn 1 region are accommodated
with essentially no change to the turn structure in the G19
mutant background.
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Figure 5.
Figure 5. (Upper panel) Relaxed stereodiagram of an overlay of
the turn 1 (CPK color scheme) and turn 5 (gray) regions in
wild-type FGF-1 (PDB accession 1JQZ). (Lower panel) Relaxed
stereo diagram of an overlay of the turn 1 (CPK color scheme)
and turn 5 (gray) regions in the S17T/N18T/ G19
and E60
mutants, respectively. The structural similarity of these
symmetry-related turns is retained as they are converted from
type I 4:6 to type I 3:5 turns.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2006,
62,
686-697)
copyright 2006.
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