1h8k: Difference between revisions
New page: left|200px<br /><applet load="1h8k" size="450" color="white" frame="true" align="right" spinBox="true" caption="1h8k, resolution 2.7Å" /> '''A-SPECTRIN SH3 DOMAIN... |
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[[Image:1h8k.gif|left|200px]]<br /><applet load="1h8k" size=" | [[Image:1h8k.gif|left|200px]]<br /><applet load="1h8k" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1h8k, resolution 2.7Å" /> | caption="1h8k, resolution 2.7Å" /> | ||
'''A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V53I, V58L MUTANT'''<br /> | '''A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V53I, V58L MUTANT'''<br /> | ||
==Overview== | ==Overview== | ||
We have designed de novo 13 divergent spectrin SH3 core sequences to | 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. | ||
==About this Structure== | ==About this Structure== | ||
1H8K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http:// | 1H8K is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H8K OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Serrano, L.]] | [[Category: Serrano, L.]] | ||
[[Category: Vega, M | [[Category: Vega, M C.]] | ||
[[Category: actin-binding]] | [[Category: actin-binding]] | ||
[[Category: calmodulin-binding]] | [[Category: calmodulin-binding]] | ||
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[[Category: sh3-domain]] | [[Category: sh3-domain]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:58:38 2008'' | ||
Revision as of 13:58, 21 February 2008
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A-SPECTRIN SH3 DOMAIN A11V, V23L, M25V, V53I, V58L MUTANT
OverviewOverview
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.
About this StructureAbout this Structure
1H8K is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.
ReferenceReference
Conformational strain in the hydrophobic core and its implications for protein folding and design., Ventura S, Vega MC, Lacroix E, Angrand I, Spagnolo L, Serrano L, Nat Struct Biol. 2002 Jun;9(6):485-93. PMID:12006985
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