PDBsum entry 1n0a

De novo protein

PDB id: 1n0a

Contents

Protein chain

13 a.a.

PDB id:

1n0a

Name:

De novo protein

Title:

Turn stability in beta-hairpin peptides: 3:5 type i g1 bulge turns

Structure:

Bhpw_pdg, beta-hairpin peptide. Chain: a. Engineered: yes

Source:

Synthetic: yes. Other_details: the peptide was chemically synthesized.

NMR struc:

21 models

Authors:

T.Blandl,A.G.Cochran,N.J.Skelton

Key ref:

T.Blandl et al. (2003). Turn stability in beta-hairpin peptides: Investigation of peptides containing 3:5 type I G1 bulge turns. Protein Sci, 12, 237-247. PubMed id: 12538887 DOI: 10.1110/ps.0228603

Date:

11-Oct-02 Release date: 21-Oct-03

Protein chain

No UniProt id for this chain

Struc: 12 a.a.

DOI no: 10.1110/ps.0228603

Protein Sci 12:237-247 (2003)

PubMed id: 12538887

Turn stability in beta-hairpin peptides: Investigation of peptides containing 3:5 type I G1 bulge turns.

T.Blandl, A.G.Cochran, N.J.Skelton.

ABSTRACT

The turn-forming ability of a series of three-residue sequences was investigated by substituting them into a well-characterized beta-hairpin peptide. The starting scaffold, bhpW, is a disulfide-cyclized 10-residue peptide that folds into a stable beta-hairpin with two antiparallel strands connected by a two-residue reverse turn. Substitution of the central two residues with the three-residue test sequences leads to less stable hairpins, as judged by thiol-disulfide equilibrium measurements. However, analysis of NMR parameters indicated that each molecule retains a significant folded population, and that the type of turn adopted by the three-residue sequence is the same in all cases. The solution structure of a selected peptide with a PDG turn contained an antiparallel beta-hairpin with a 3:5 type I + G1 bulge turn. Analysis of the energetic contributions of individual turn residues in the series of peptides indicates that substitution effects have significant context dependence, limiting the predictive power of individual amino acid propensities for turn formation. The most stable and least stable sequences were also substituted into a more stable disulfide-cyclized scaffold and a linear beta-hairpin scaffold. The relative stabilities remained the same, suggesting that experimental measurements in the bhpW context are a useful way to evaluate turn stability for use in protein design projects. Moreover, these scaffolds are capable of displaying a diverse set of turns, which can be exploited for the mimicry of protein loops or for generating libraries of reverse turns.

Selected figure(s)

Figure 1.
Figure 1. Structure of PDG and comparison to bhpW. (A) An ensemble of 20 PDG structures (mean backbone RMSD to the mean structure = 0.29 ± 0.05 Å). Side chain of N6 is omitted for clarity, and E4 and K8 are only shown to the C^ß. (B) Superposition of the minimized mean structures of PDG (blue) onto bhpW (magenta). Side chains between residues 4 and 8 are omitted for clarity. Backbone heavy atom RMSD of the strands (residues 1-3, 9-11) is 0.36 Å.

Figure 4.
Figure 4. Comparison of PDG and protein hairpins. (A) Superposition of PDG (shown as in Fig. 1 Go-) on 15 protein hairpins shown in gray, with only backbone and proline side chains shown. The backbone heavy atom RMSD = 1.29 ± 0.65 Å. (B) Superposition of PDG (blue ribbon) onto a hairpin (highlighted in red) in lipoxygenase (1LOX). Surrounding backbone segments of the crystal structure of the protein are shown as gray ribbon. Side chains are shown only for C1, W3, E4, P5, N6, L9, and C11 in PDG and the corresponding residues in lipoxygenase. The backbone heavy atom RMSD of 1LOX residues 305-313 (KLQPDGKLM) and PDG residues 2-10 is 0.43 Å.

The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 237-247) copyright 2003.

Figures were selected by the author.