2jm0: Difference between revisions

Line 4:

==Overview==

We report the first high-resolution structure for a protein containing a, fluorinated side chain. Recently we carried out a systematic evaluation of, phenylalanine to pentafluorophenylalanine (Phe --> F(5)-Phe) mutants for, the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic, core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F(5)-Phe mutations are interesting because, aryl-perfluoroaryl interactions of optimal geometry are intrinsically more, favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl, interactions, and because perfluoroaryl units are more hydrophobic than, are analogous aryl units. Only one mutation, Phe10 --> F(5)-Phe, was found, to provide enhanced tertiary structural stability relative to the native, core (by approximately 1 kcal/mol, according to guanidinium chloride, denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain, packing relative to the wild type. Thus, although Phe --> F(5)-Phe, mutations offer the possibility of greater tertiary structural stability, from side chain-side chain attraction and/or side chain desolvation, the, constraints associated with the native c-VHP fold apparently prevent the, modified polypeptide from taking advantage of this possibility. Our, findings are important because they complement several studies that have, shown that fluorination of saturated side chain carbon atoms can provide, enhanced conformational stability.

We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe --> F(5)-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --> F(5)-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 --> F(5)-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by approximately 1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe --> F(5)-Phe mutations offer the possibility of greater tertiary structural stability from side chain-side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability.

==About this Structure==

Line 12:

Solution structure of a small protein containing a fluorinated side chain in the core., Cornilescu G, Hadley EB, Woll MG, Markley JL, Gellman SH, Cornilescu CC, Protein Sci. 2007 Jan;16(1):14-9. Epub 2006 Nov 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17123960 17123960]

[[Category: Single protein]]

[[Category: Cornilescu, C.C.]]

[[Category: Cornilescu, C C.]]

[[Category: Cornilescu, G.]]

[[Category: Gellman, S.H.]]

[[Category: Gellman, S H.]]

[[Category: Hadley, E.B.]]

[[Category: Hadley, E B.]]

[[Category: Markley, J.L.]]

[[Category: Markley, J L.]]

[[Category: chicken villin headpiece]]

[[Category: fluorinated phe]]

[[Category: vhp]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 14~~:53:09 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:03:50 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==Overview==
-We report the first high-resolution structure for a protein containing a, fluorinated side chain. Recently we carried out a systematic evaluation of, phenylalanine to pentafluorophenylalanine (Phe --&gt; F(5)-Phe) mutants for, the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic, core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --&gt; F(5)-Phe mutations are interesting because, aryl-perfluoroaryl interactions of optimal geometry are intrinsically more, favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl, interactions, and because perfluoroaryl units are more hydrophobic than, are analogous aryl units. Only one mutation, Phe10 --&gt; F(5)-Phe, was found, to provide enhanced tertiary structural stability relative to the native, core (by approximately 1 kcal/mol, according to guanidinium chloride, denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain, packing relative to the wild type. Thus, although Phe --&gt; F(5)-Phe, mutations offer the possibility of greater tertiary structural stability, from side chain-side chain attraction and/or side chain desolvation, the, constraints associated with the native c-VHP fold apparently prevent the, modified polypeptide from taking advantage of this possibility. Our, findings are important because they complement several studies that have, shown that fluorination of saturated side chain carbon atoms can provide, enhanced conformational stability.
+We report the first high-resolution structure for a protein containing a fluorinated side chain. Recently we carried out a systematic evaluation of phenylalanine to pentafluorophenylalanine (Phe --&gt; F(5)-Phe) mutants for the 35-residue chicken villin headpiece subdomain (c-VHP), the hydrophobic core of which features a cluster of three Phe side chains (residues 6, 10, and 17). Phe --&gt; F(5)-Phe mutations are interesting because aryl-perfluoroaryl interactions of optimal geometry are intrinsically more favorable than either aryl-aryl or perfluoroaryl-perfluoroaryl interactions, and because perfluoroaryl units are more hydrophobic than are analogous aryl units. Only one mutation, Phe10 --&gt; F(5)-Phe, was found to provide enhanced tertiary structural stability relative to the native core (by approximately 1 kcal/mol, according to guanidinium chloride denaturation studies). The NMR structure of this mutant, described here, reveals very little variation in backbone conformation or side chain packing relative to the wild type. Thus, although Phe --&gt; F(5)-Phe mutations offer the possibility of greater tertiary structural stability from side chain-side chain attraction and/or side chain desolvation, the constraints associated with the native c-VHP fold apparently prevent the modified polypeptide from taking advantage of this possibility. Our findings are important because they complement several studies that have shown that fluorination of saturated side chain carbon atoms can provide enhanced conformational stability.
 ==About this Structure==
@@ Line 12: / Line 12: @@
 Solution structure of a small protein containing a fluorinated side chain in the core., Cornilescu G, Hadley EB, Woll MG, Markley JL, Gellman SH, Cornilescu CC, Protein Sci. 2007 Jan;16(1):14-9. Epub 2006 Nov 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17123960 17123960]
 [[Category: Single protein]]
-[[Category: Cornilescu, C.C.]]
+[[Category: Cornilescu, C C.]]
 [[Category: Cornilescu, G.]]
-[[Category: Gellman, S.H.]]
+[[Category: Gellman, S H.]]
-[[Category: Hadley, E.B.]]
+[[Category: Hadley, E B.]]
-[[Category: Markley, J.L.]]
+[[Category: Markley, J L.]]
 [[Category: chicken villin headpiece]]
 [[Category: fluorinated phe]]
 [[Category: vhp]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:53:09 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:03:50 2008''