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PDBsum entry 1ud7
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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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Solution structure and dynamics of a designed hydrophobic core variant of ubiquitin.
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Authors
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E.C.Johnson,
G.A.Lazar,
J.R.Desjarlais,
T.M.Handel.
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Ref.
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Structure Fold Des, 1999,
7,
967-976.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: The recent merger of computation and protein design has resulted in
a burst of success in the generation of novel proteins with native-like
properties. A critical component of this coupling between theory and experiment
is a detailed analysis of the structures and stabilities of designed proteins to
assess and improve the accuracy of design algorithms. RESULTS: Here we report
the solution structure of a hydrophobic core variant of ubiquitin, referred to
as 1D7, which was designed with the core-repacking algorithm ROC. As a measure
of conformational specificity, we also present amide exchange protection factors
and backbone and sidechain dynamics. The results indicate that 1D7 is similar to
wild-type (WT) ubiquitin in backbone structure and degree of conformational
specificity. We also observe a good correlation between experimentally
determined sidechain structures and those predicted by ROC. However, evaluation
of the core sidechain conformations indicates that, in general, 1D7 has more
sidechains in less statistically favorable conformations than WT. CONCLUSIONS:
Our results provide an explanation for the lower stability of 1D7 compared to
WT, and suggest modifications to design algorithms that may improve the accuracy
with which structure and stability are predicted. The results also demonstrate
that core packing can affect conformational flexibility in subtle ways that are
likely to be important for the design of function and protein-ligand
interactions.
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Figure 1.
Figure 1. Structures of 1D7 versus WT. (a) Stereoview of an
ensemble of the 20 lowest energy structures of 1D7. Sidechains
of core residues are displayed in green and the N and C termini
are labeled. (b) Superposition of the structure of 1D7 closest
to the mean (blue) with the crystal structure (red; accession
code 1UBI [15]) the coordinates of which were used for the
design. (c) Residual dipolar NH couplings of partially oriented
1D7 (y axis) versus WT ubiquitin (x axis) in DMPC:DHPC bicelles
[16]. WT dipolar couplings were taken from Cornilescu et al.
[25]. The difference in the range of dipolar couplings between
the two samples is due to differences in bicelle content.
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The above figure is
reprinted
by permission from Cell Press:
Structure Fold Des
(1999,
7,
967-976)
copyright 1999.
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