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1zcn

From Proteopedia

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[[Image:1zcn.gif|left|200px]]
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{{Seed}}
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[[Image:1zcn.png|left|200px]]
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{{STRUCTURE_1zcn| PDB=1zcn | SCENE= }}
{{STRUCTURE_1zcn| PDB=1zcn | SCENE= }}
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'''human Pin1 Ng mutant'''
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===human Pin1 Ng mutant===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_16807295}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 16807295 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16807295}}
==About this Structure==
==About this Structure==
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[[Category: Type i beta-turn]]
[[Category: Type i beta-turn]]
[[Category: Ww domain]]
[[Category: Ww domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jun 5 09:56:15 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 11:27:26 2008''

Revision as of 08:27, 28 July 2008

Template:STRUCTURE 1zcn

human Pin1 Ng mutant

Template:ABSTRACT PUBMED 16807295

About this Structure

1ZCN is a Single protein structure of sequence from Homo sapiens. 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

Page seeded by OCA on Mon Jul 28 11:27:26 2008

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