2JM0

Solution structure of chicken villin headpiece subdomain containing a fluorinated side chain in the core

Summary for 2JM0

• Entry DOI: 10.2210/pdb2jm0/pdb
• NMR Information: BMRB: 15000
• Descriptor: Villin-1 (1 entity in total)
• Functional Keywords: fluorinated phe, vhp, chicken villin headpiece, structural protein
• Cellular location: Cytoplasm, cytoskeleton: P02640
• Total number of polymer chains: 1
• Total formula weight: 4294.73

Authors

Cornilescu, C.C.,Cornilescu, G.,Hadley, E.B.,Gellman, S.H.,Markley, J.L. (deposition date: 2006-09-06, release date: 2006-10-17, Last modification date: 2024-11-20)

Primary citation

Cornilescu, G.,Hadley, E.B.,Woll, M.G.,Markley, J.L.,Gellman, S.H.,Cornilescu, C.C.
Solution structure of a small protein containing a fluorinated side chain in the core.
Protein Sci., 16:14-19, 2007

PubMed Abstract: 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.

PubMed: 17123960
DOI: 10.1110/ps.062557707

Experimental method

SOLUTION NMR