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PDBsum entry 1e6h
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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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Conformational strain in the hydrophobic core and its implications for protein folding and design.
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Authors
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S.Ventura,
M.C.Vega,
E.Lacroix,
I.Angrand,
L.Spagnolo,
L.Serrano.
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Ref.
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Nat Struct Biol, 2002,
9,
485-493.
[DOI no: ]
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PubMed id
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Abstract
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We have designed de novo 13 divergent spectrin SH3 core sequences to determine
their folding properties. Kinetic analysis of the variants with stability
similar to that of the wild type protein shows accelerated unfolding and
refolding rates compatible with a preferential stabilization of the transition
state. This is most likely caused by conformational strain in the native state,
as deletion of a methyl group (Ile-->Val) leads to deceleration in unfolding and
increased stability (up to 2 kcal x mol(-1)). Several of these Ile-->Val mutants
have negative phi(-U) values, indicating that some noncanonical phi(-U) values
might result from conformational strain. Thus, producing a stable protein does
not necessarily mean that the design process has been entirely successful.
Strained interactions could have been introduced, and a reduction in the buried
volume could result in a large increase in stability and a reduction in
unfolding rates.
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Figure 4.
Figure 4. Folding and unfolding kinetic curves of the WT,
spectrin SH3 and core mutants.
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Figure 5.
Figure 5. Stereo view of the omit map of the core residues.
a, Best4; b, C8A; and c, C8A-I25V mutants contoured at 1  level.
The orientation of the hydrophobic core is identical to those in
Fig. 6.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2002,
9,
485-493)
copyright 2002.
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Secondary reference #1
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Title
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Crystal structure of a src-Homology 3 (sh3) domain.
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Authors
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A.Musacchio,
M.Noble,
R.Pauptit,
R.Wierenga,
M.Saraste.
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Ref.
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Nature, 1992,
359,
851-855.
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PubMed id
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