PDBsum entry 2jm0

Structural protein

PDB id: 2jm0

Contents

Protein chain

35 a.a. *

* Residue conservation analysis

PDB id:

2jm0

Name:

Structural protein

Title:

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

Structure:

Villin-1. Chain: a. Fragment: residues 792-826. Engineered: yes

Source:

Synthetic: yes. Other_details: this sequence occurs naturally in gallus gallus (chicken).

NMR struc:

20 models

Authors:

C.C.Cornilescu,G.Cornilescu,E.B.Hadley,S.H.Gellman,J.L.Markley

Key ref:

G.Cornilescu et al. (2007). Solution structure of a small protein containing a fluorinated side chain in the core. Protein Sci, 16, 14-19. PubMed id: 17123960 DOI: 10.1110/ps.062557707

Date:

06-Sep-06 Release date: 17-Oct-06

Protein chain

P02640  (VILI_CHICK) -  Villin-1 from Gallus gallus

Seq: 826 a.a.

Struc: 35 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

DOI no: 10.1110/ps.062557707

Protein Sci 16:14-19 (2007)

PubMed id: 17123960

Solution structure of a small protein containing a fluorinated side chain in the core.

G.Cornilescu, E.B.Hadley, M.G.Woll, J.L.Markley, S.H.Gellman, C.C.Cornilescu.

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.

Selected figure(s)

Figure 1.
Figure 1. Sequence comparison for cVHP and the F5-Phe-containing

Figure 4.
Figure 4. 1 H-- 15 N HSQC of data for the F5-Phe-containing mutant of cVHP (unlabeled sample).

The above figures are reprinted by permission from the Protein Society: Protein Sci (2007, 16, 14-19) copyright 2007.

Figures were selected by an automated process.