1zcn: Difference between revisions
New page: left|200px<br /> <applet load="1zcn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zcn, resolution 1.9Å" /> '''human Pin1 Ng mutant... |
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[[Image:1zcn.gif|left|200px]]<br /> | [[Image:1zcn.gif|left|200px]]<br /><applet load="1zcn" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="1zcn, resolution 1.9Å" /> | caption="1zcn, resolution 1.9Å" /> | ||
'''human Pin1 Ng mutant'''<br /> | '''human Pin1 Ng 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== | ||
1ZCN 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 PO4 and 1PE as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | 1ZCN 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=PO4:'>PO4</scene> and <scene name='pdbligand=1PE:'>1PE</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1ZCN OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Peptidylprolyl isomerase]] | [[Category: Peptidylprolyl isomerase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bowman, M | [[Category: Bowman, M E.]] | ||
[[Category: Dendel, G.]] | [[Category: Dendel, G.]] | ||
[[Category: Gruebele, M.]] | [[Category: Gruebele, M.]] | ||
[[Category: Jager, M.]] | [[Category: Jager, M.]] | ||
[[Category: Kelly, J | [[Category: Kelly, J W.]] | ||
[[Category: Nguyen, H.]] | [[Category: Nguyen, H.]] | ||
[[Category: Noel, J | [[Category: Noel, J P.]] | ||
[[Category: Zhang, Y.]] | [[Category: Zhang, Y.]] | ||
[[Category: 1PE]] | [[Category: 1PE]] | ||
| Line 28: | Line 27: | ||
[[Category: ww domain]] | [[Category: ww domain]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:14:14 2008'' | ||
Revision as of 14:14, 21 February 2008
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human Pin1 Ng 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
1ZCN is a Single protein structure of sequence from Homo sapiens with PO4 and 1PE as ligands. 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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