2f21
From Proteopedia
(New page: 200px<br /> <applet load="2f21" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f21, resolution 1.5Å" /> '''human Pin1 Fip mutan...) |
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| - | [[Image:2f21.gif|left|200px]]<br /> | + | [[Image:2f21.gif|left|200px]]<br /><applet load="2f21" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2f21" size=" | + | |
caption="2f21, resolution 1.5Å" /> | caption="2f21, resolution 1.5Å" /> | ||
'''human Pin1 Fip mutant'''<br /> | '''human Pin1 Fip mutant'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Protein folding barriers result from a combination of factors including | + | Protein folding barriers result from a combination of factors including unavoidable energetic frustration from nonnative interactions, natural variation and selection of the amino acid sequence for function, and/or selection pressure against aggregation. The rate-limiting step for human Pin1 WW domain folding is the formation of the loop 1 substructure. The native conformation of this six-residue loop positions side chains that are important for mediating protein-protein interactions through the binding of Pro-rich sequences. Replacement of the wild-type loop 1 primary structure by shorter sequences with a high propensity to fold into a type-I' beta-turn conformation or the statistically preferred type-I G1 bulge conformation accelerates WW domain folding by almost an order of magnitude and increases thermodynamic stability. However, loop engineering to optimize folding energetics has a significant downside: it effectively eliminates WW domain function according to ligand-binding studies. The energetic contribution of loop 1 to ligand binding appears to have evolved at the expense of fast folding and additional protein stability. Thus, the two-state barrier exhibited by the wild-type human Pin1 WW domain principally results from functional requirements, rather than from physical constraints inherent to even the most efficient loop formation process. |
==About this Structure== | ==About this Structure== | ||
| - | 2F21 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 1PE as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] Full crystallographic information is available from [http:// | + | 2F21 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=1PE:'>1PE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F21 OCA]. |
==Reference== | ==Reference== | ||
| Line 15: | Line 14: | ||
[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bowman, M | + | [[Category: Bowman, M E.]] |
[[Category: Jager, M.]] | [[Category: Jager, M.]] | ||
| - | [[Category: Kelly, J | + | [[Category: Kelly, J W.]] |
| - | [[Category: Noel, J | + | [[Category: Noel, J P.]] |
[[Category: Zhang, Y.]] | [[Category: Zhang, Y.]] | ||
[[Category: 1PE]] | [[Category: 1PE]] | ||
| Line 24: | Line 23: | ||
[[Category: ww domain]] | [[Category: ww domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:55 2008'' |
Revision as of 15:16, 21 February 2008
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human Pin1 Fip mutant
Overview
Protein folding barriers result from a combination of factors including unavoidable energetic frustration from nonnative interactions, natural variation and selection of the amino acid sequence for function, and/or selection pressure against aggregation. The rate-limiting step for human Pin1 WW domain folding is the formation of the loop 1 substructure. The native conformation of this six-residue loop positions side chains that are important for mediating protein-protein interactions through the binding of Pro-rich sequences. Replacement of the wild-type loop 1 primary structure by shorter sequences with a high propensity to fold into a type-I' beta-turn conformation or the statistically preferred type-I G1 bulge conformation accelerates WW domain folding by almost an order of magnitude and increases thermodynamic stability. However, loop engineering to optimize folding energetics has a significant downside: it effectively eliminates WW domain function according to ligand-binding studies. The energetic contribution of loop 1 to ligand binding appears to have evolved at the expense of fast folding and additional protein stability. Thus, the two-state barrier exhibited by the wild-type human Pin1 WW domain principally results from functional requirements, rather than from physical constraints inherent to even the most efficient loop formation process.
About this Structure
2F21 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Peptidylprolyl isomerase, with EC number 5.2.1.8 Full crystallographic information is available from OCA.
Reference
Structure-function-folding relationship in a WW domain., Jager M, Zhang Y, Bieschke J, Nguyen H, Dendle M, Bowman ME, Noel JP, Gruebele M, Kelly JW, Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10648-53. Epub 2006 Jun 28. PMID:16807295
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