2f21: Difference between revisions

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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="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="2f21, resolution 1.5Å" />

'''human Pin1 Fip mutant'''<br />

==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.

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 [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://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2F21 OCA].

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==

Line 15:

Line 14:

[[Category: Peptidylprolyl isomerase]]

[[Category: Single protein]]

[[Category: Bowman, M.E.]]

[[Category: Bowman, M E.]]

[[Category: Jager, M.]]

[[Category: Kelly, J.W.]]

[[Category: Kelly, J W.]]

[[Category: Noel, J.P.]]

[[Category: Noel, J P.]]

[[Category: Zhang, Y.]]

[[Category: 1PE]]

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[[Category: ww domain]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12~~ 21:58:~~36 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:55 2008''

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@@ Line 1: / Line 1: @@
-[[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="450" color="white" frame="true" align="right" spinBox="true"
 caption="2f21, resolution 1.5&Aring;" />
 '''human Pin1 Fip mutant'''<br />
 ==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.
+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==
-F21 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F21 OCA].
+F21 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==
@@ Line 15: / Line 14: @@
 [[Category: Peptidylprolyl isomerase]]
 [[Category: Single protein]]
-[[Category: Bowman, M.E.]]
+[[Category: Bowman, M E.]]
 [[Category: Jager, M.]]
-[[Category: Kelly, J.W.]]
+[[Category: Kelly, J W.]]
-[[Category: Noel, J.P.]]
+[[Category: Noel, J P.]]
 [[Category: Zhang, Y.]]
 [[Category: 1PE]]
@@ Line 24: / Line 23: @@
 [[Category: ww domain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 21:58:36 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:55 2008''