1sif
From Proteopedia
(New page: 200px<br /> <applet load="1sif" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sif, resolution 2.18Å" /> '''Crystal structure o...) |
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| - | [[Image:1sif.gif|left|200px]]<br /> | + | [[Image:1sif.gif|left|200px]]<br /><applet load="1sif" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1sif, resolution 2.18Å" /> | caption="1sif, resolution 2.18Å" /> | ||
'''Crystal structure of a multiple hydrophobic core mutant of ubiquitin'''<br /> | '''Crystal structure of a multiple hydrophobic core mutant of ubiquitin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The stability, dynamic, and structural properties of ubiquitin and two | + | The stability, dynamic, and structural properties of ubiquitin and two multiple hydrophobic core mutants were studied. One of the mutants (U4) has seven substitutions in the hydrophobic core (M1L, I3L, V5I, I13F, L15V, V17M, and V26L). On average, its side chains are larger than the wild-type, and it can thus be thought of as having an overpacked core. The other mutant (U7) has two substitutions (I3V and I13V). On average, it has smaller side chains than the wild-type, and it can therefore be considered to be underpacked. The three proteins are well-folded and show similar backbone dynamics (T(1), T(2), and HNOE values), indicating that the regular secondary structure extends over the same residue ranges. The crystallographic structure of U4 was determined. The final R(factor) and R(free) are 0.198 and 0.248, respectively, at 2.18 A resolution. The structure of U4 is very similar to wild-type ubiquitin. Remarkably, there are almost no changes in the positions of the C(alpha) atoms along the entire backbone, and the hydrogen-bonding network is maintained. The mutations of the hydrophobic core are accommodated by small movements of side chains in the core of mutated and nonmutated residues. Unfolding and refolding kinetic studies revealed that U4 unfolds with the highest rates; however, its refolding rate constants are very similar to those of the wild-type protein. Conversely, U7 seems to be the most destabilized protein; its refolding rate constant is smaller than the other two proteins. This was confirmed by stopped-flow techniques and by H/D exchange methodologies. This work illustrates the possibility of repacking the hydrophobic core of small proteins and has important implications in the de novo design of stable proteins. |
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| + | ==Disease== | ||
| + | Known disease associated with this structure: Cleft palate, isolated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191339 191339]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 1SIF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1SIF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SIF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Benitez-Cardoza, C | + | [[Category: Benitez-Cardoza, C G.]] |
[[Category: Hirshberg, M.]] | [[Category: Hirshberg, M.]] | ||
| - | [[Category: Jackson, S | + | [[Category: Jackson, S E.]] |
[[Category: Stott, K.]] | [[Category: Stott, K.]] | ||
| - | [[Category: Went, H | + | [[Category: Went, H M.]] |
| - | [[Category: Woolfson, D | + | [[Category: Woolfson, D N.]] |
[[Category: folding]] | [[Category: folding]] | ||
[[Category: hydrophobic mutants]] | [[Category: hydrophobic mutants]] | ||
[[Category: stability]] | [[Category: stability]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:49 2008'' |
Revision as of 13:01, 21 February 2008
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Crystal structure of a multiple hydrophobic core mutant of ubiquitin
Contents |
Overview
The stability, dynamic, and structural properties of ubiquitin and two multiple hydrophobic core mutants were studied. One of the mutants (U4) has seven substitutions in the hydrophobic core (M1L, I3L, V5I, I13F, L15V, V17M, and V26L). On average, its side chains are larger than the wild-type, and it can thus be thought of as having an overpacked core. The other mutant (U7) has two substitutions (I3V and I13V). On average, it has smaller side chains than the wild-type, and it can therefore be considered to be underpacked. The three proteins are well-folded and show similar backbone dynamics (T(1), T(2), and HNOE values), indicating that the regular secondary structure extends over the same residue ranges. The crystallographic structure of U4 was determined. The final R(factor) and R(free) are 0.198 and 0.248, respectively, at 2.18 A resolution. The structure of U4 is very similar to wild-type ubiquitin. Remarkably, there are almost no changes in the positions of the C(alpha) atoms along the entire backbone, and the hydrogen-bonding network is maintained. The mutations of the hydrophobic core are accommodated by small movements of side chains in the core of mutated and nonmutated residues. Unfolding and refolding kinetic studies revealed that U4 unfolds with the highest rates; however, its refolding rate constants are very similar to those of the wild-type protein. Conversely, U7 seems to be the most destabilized protein; its refolding rate constant is smaller than the other two proteins. This was confirmed by stopped-flow techniques and by H/D exchange methodologies. This work illustrates the possibility of repacking the hydrophobic core of small proteins and has important implications in the de novo design of stable proteins.
Disease
Known disease associated with this structure: Cleft palate, isolated OMIM:[191339]
About this Structure
1SIF is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Exploring sequence/folding space: folding studies on multiple hydrophobic core mutants of ubiquitin., Benitez-Cardoza CG, Stott K, Hirshberg M, Went HM, Woolfson DN, Jackson SE, Biochemistry. 2004 May 11;43(18):5195-203. PMID:15122885
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